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Comparing regression-based approaches for identifying microbial functional groups. 比较基于回归的微生物功能群鉴定方法。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-30 DOI: 10.1088/1478-3975/addc2a
Fang Yu, Mikhail Tikhonov

Microbial communities are composed of functionally integrated taxa, and identifying which taxa contribute to a given ecosystem function is essential for predicting community behaviors. This study compares the effectiveness of a previously proposed method for identifying 'functional taxa,' ensemble quotient optimization (EQO), to a potentially simpler approach based on the least absolute shrinkage and selection operator (LASSO). In contrast to LASSO, EQO uses a binary prior on coefficients, assuming uniform contribution strength across taxa. Using synthetic datasets with increasingly realistic structure, we demonstrate that EQO's strong prior enables it to perform better in low-data regime. However, LASSO's flexibility and efficiency can make it preferable as data complexity increases. Our results detail the favorable conditions for EQO and emphasize LASSO as a viable alternative.

微生物群落是由功能整合的分类群组成的,确定哪些分类群对给定的生态系统功能有贡献是预测群落行为的必要条件。本研究比较了先前提出的识别“功能分类群”的方法,即集合商优化(EQO)与基于最小绝对收缩和选择算子(LASSO)的潜在更简单的方法的有效性。与LASSO相比,EQO对系数使用二元先验,假设跨分类群的贡献强度是一致的。使用结构越来越真实的合成数据集,我们证明了EQO的强先验使其在低数据状态下表现更好。然而,随着数据复杂性的增加,LASSO的灵活性和效率可以使其成为首选。我们的结果详细说明了EQO的有利条件,并强调LASSO是可行的替代方案。
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引用次数: 0
Effect of membrane tension on pore formation induced by antimicrobial peptides and other membrane-active peptides. 膜张力对抗菌肽和其他膜活性肽诱导的孔形成的影响。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-06 DOI: 10.1088/1478-3975/add071
Marzuk Ahmed, Md Masum Billah, Masahito Yamazaki

Membrane tension plays an important role in various aspects of the dynamics and functions of cells. Here, we review recent studies of the effect of membrane tension on pore formation in lipid bilayers and pore formation induced by membrane-active peptides (MAPs) including antimicrobial peptides (AMPs). For this purpose, the micropipette aspiration method using a patch of cell membrane/lipid bilayers and a giant unilamellar vesicle (GUV)/a total cell, and the application of osmotic pressure (Π) to suspensions of large unilamellar vesicles (LUVs) have been used. However, these conventional methods have some drawbacks for the investigation of the effect of membrane tension on the actions of MAPs such as AMPs. Recently, to overcome these drawbacks, a new Π method using GUVs has been developed. Here, we focus on this Π method as a new technique for revealing the effect of membrane tension on the MAPs-induced pore formation. Firstly, we review studies of the effect of membrane tension on pore formation in lipid bilayers as determined by conventional methods. Secondly, after a brief review of studies of the effect of Π on LUVs, we describe the estimation of membrane tension in GUVs induced by Π and the Π-induced pore formation. Thirdly, after a review of the effect of membrane tension on the MAPs-induced pore formation as obtained by the conventional methods, we describe an application of the Π method to studies of the effect of membrane tension on AMP-induced pore formation. Finally, we discuss the advantages of the Π method over conventional methods and consider future perspectives.

膜张力在细胞动力学和功能的各个方面起着重要的作用。本文综述了膜张力对脂质双分子层孔隙形成的影响以及膜活性肽(MAPs)(包括抗菌肽(amp))诱导的孔隙形成的最新研究。为此,采用微管抽吸法,利用细胞膜/脂质双分子层和巨型单层囊泡(GUV)/总细胞,并应用渗透压(Π)对大单层囊泡(LUVs)悬浮液进行抽吸。然而,这些传统的方法在研究膜张力对map(如amp)作用的影响时存在一些缺陷。最近,为了克服这些缺点,开发了一种使用guv的Π新方法。在这里,我们将重点放在Π方法上,作为一种揭示膜张力对map诱导的孔隙形成影响的新技术。首先,我们回顾了膜张力对脂质双分子层孔隙形成的影响。其次,在简要回顾了Π对luv影响的研究之后,我们描述了Π诱导的guv中膜张力的估计和Π-induced孔隙形成。第三,在回顾了膜张力对传统方法获得的map诱导孔隙形成的影响后,我们描述了Π方法在研究膜张力对amp诱导孔隙形成的影响中的应用。最后,我们讨论了Π方法相对于传统方法的优势,并考虑了未来的前景。
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引用次数: 0
Representation of high-dimensional cell morphology and morphodynamics in 2D latent space. 二维潜伏空间中高维细胞形态和形态动力学的表征。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-24 DOI: 10.1088/1478-3975/adcd37
Christian Cunningham, Bo Sun

The morphology and morphodynamics of cells as important biomarkers of the cellular state are widely appreciated in both fundamental research and clinical applications. Quantification of cell morphology often requires a large number of geometric measures that form a high-dimensional feature vector. This mathematical representation creates barriers to communicating, interpreting, and visualizing data. Here, we develop a deep learning-based algorithm to project 13-dimensional (13D) morphological feature vectors into 2-dimensional (2D) morphological latent space (MLS). We show that the projection has less than 5% information loss and separates the different migration phenotypes of metastatic breast cancer cells. Using the projection, we demonstrate the phenotype-dependent motility of breast cancer cells in the 3D extracellular matrix, and the continuous cell state change upon drug treatment. We also find that dynamics in the 2D MLS quantitatively agrees with the morphodynamics of cells in the 13D feature space, preserving the diffusive power and the Lyapunov exponent of cell shape fluctuations even though the dimensional reduction projection is highly nonlinear. Our results suggest that MLS is a powerful tool to represent and understand the cell morphology and morphodynamics.

细胞的形态和形态动力学作为细胞状态的重要生物标志物,在基础研究和临床应用中都得到了广泛的重视。细胞形态的量化通常需要大量的几何测量来形成一个高维特征向量。这种数学表示为交流、解释和可视化数据创造了障碍。在这里,我们开发了一种基于深度学习的算法,将13维(13D)形态特征向量投影到2维(2D)形态潜在空间(MLS)中。我们表明,该投影具有小于5%的信息丢失,并分离了转移性乳腺癌细胞的不同迁移表型。利用投影,我们展示了乳腺癌细胞在3D细胞外基质中的表型依赖性运动,以及药物治疗后细胞状态的连续变化。我们还发现,二维MLS中的动力学在数量上与13D特征空间中的细胞形态动力学一致,即使降维投影是高度非线性的,也保留了细胞形状波动的扩散功率和Lyapunov指数。我们的研究结果表明,MLS是表征和理解细胞形态和形态动力学的有力工具。
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引用次数: 0
Fluctuation-driven synergy, redundancy, signal to noise ratio and error correction in protein allostery. 蛋白质变构中波动驱动的协同、冗余、信噪比和纠错。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-05 DOI: 10.1088/1478-3975/adb9af
Burak Erman

This study explores the relationship between residue fluctuations and molecular communication in proteins, emphasizing the role of these dynamics in allosteric regulation. We employ computational tools including the Gaussian network model, mutual information, and interaction information, to analyze how stochastic interactions among residues contribute to functional interactions while also introducing noise. Our approach is based on the postulate that residues experience continuous stochastic bombardment from impulses generated by their neighbors, forming a complex network characterized by small-world scaling topology. By mapping these interactions through the Kirchhoff matrix framework, we demonstrate how conserved correlations enhance signaling pathways and provide stability against noise-like fluctuations. Notably, we highlight the importance of selecting relevant eigenvalues to optimize the signal-to-noise ratio in our analyses, a topic that has yet to be thoroughly investigated in the context of residue fluctuations. This work underscores the significance of viewing proteins as adaptive information processing systems, and emphasizes the fundamental mechanisms of biological information processing. The basic idea of this paper is the following: given two interacting residues on an allosteric path, what are the contributions of the remaining residues on this interaction. This naturally leads to the concept of synergy, redundancy and noise in proteins, which we analyze in detail for three proteins CheY, tyrosine phosphatase andβ-lactoglobulin.

本研究探讨了蛋白质中残基波动与分子通讯之间的关系,强调了这些动态在变构调节中的作用。我们使用计算工具,包括高斯网络模型、互信息和相互作用信息,来分析残基之间的随机相互作用如何在引入噪声的同时促进功能相互作用。我们的方法是基于残基经历相邻脉冲连续随机轰击的假设,形成一个具有小世界尺度拓扑特征的复杂网络。通过Kirchhoff矩阵框架映射这些相互作用,我们证明了保守相关性如何增强信号通路并提供抗噪声波动的稳定性。值得注意的是,在我们的分析中,我们强调了选择相关特征值以优化信噪比的重要性,这一主题尚未在残差波动的背景下进行彻底研究。这项工作强调了将蛋白质视为自适应信息处理系统的重要性,并强调了生物信息处理的基本机制。本文的基本思想是:给定变构路径上的两个相互作用的残基,剩余残基对这个相互作用的贡献是什么?这自然导致了蛋白质协同、冗余和噪声的概念,我们详细分析了三种蛋白质CheY、酪氨酸磷酸酶和β-乳球蛋白。
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引用次数: 0
STIPS algorithm enables tracking labyrinthine patterns and reveals distinct rhythmic dynamics of actin microridges. STIPS算法可以跟踪迷宫模式,揭示肌动蛋白微脊的独特节奏动态。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-03 DOI: 10.1088/1478-3975/ada862
Rajasekaran Bhavna, Mahendra Sonawane

Tracking and motion analyses of semi-flexible biopolymer networks from time-lapse microscopy images are important tools that enable quantitative measurements to unravel the dynamic and mechanical properties of biopolymers in living tissues, crucial for understanding their organization and function. Biopolymer networks are challenging to track due to continuous stochastic transitions, such as merges and splits, which cause local neighborhood rearrangements over short time and length scales. To address this, we propose the Spatio Temporal Information on Pixel Subsets algorithm to track these events by creating pixel subsets that link trajectories across frames. Using this method, we analyzed actin-enriched protrusions, or 'microridges,' which form dynamic labyrinthine patterns on squamous cell epithelial surfaces, mimicking 'active Turing-patterns.' Our results reveal two distinct actomyosin-based rhythmic dynamics in neighboring cells: a common pulsatile mechanism between 2 and 6.25 min period governing both fusion and fission events contributing to pattern maintenance, and cell area pulses predominantly exhibiting 10 min period.

从延时显微镜图像中对半柔性生物聚合物网络进行跟踪和运动分析是重要的工具,可以通过定量测量来揭示活组织中生物聚合物的动态和机械特性,这对于理解它们的组织和功能至关重要。由于连续的随机转变,如合并和分裂,导致局部邻域在短时间和长度尺度上重新排列,生物聚合物网络的跟踪具有挑战性。为了解决这个问题,我们提出了STIPS算法(像素子集的时空信息),通过创建跨帧链接轨迹的像素子集来跟踪这些事件。使用这种方法,我们分析了肌动蛋白富集的突起,或“微脊”,它们在鳞状细胞上皮表面形成动态迷宫图案,模仿“活跃的图灵模式”。我们的研究结果揭示了相邻细胞中两种截然不同的基于肌动球蛋白的节律动力学:一种共同的脉动机制,周期为2至6.25分钟,控制融合和裂变事件,有助于维持模式,而细胞区域脉冲主要表现为10分钟周期。
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引用次数: 0
Electrical homeostasis of the inner mitochondrial membrane potential. 线粒体内膜电位的电稳态。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-31 DOI: 10.1088/1478-3975/adaa47
Peyman Fahimi, Lázaro A M Castanedo, P Thomas Vernier, Chérif F Matta

The electric potential across the inner mitochondrial membrane must be maintained within certain bounds for the proper functioning of the cell. A feedback control mechanism for the homeostasis of this membrane potential is proposed whereby an increase in the electric field decreases the rate-limiting steps of the electron transport chain (ETC). An increase in trans-membrane electric field limits the rate of proton pumping to the inter-membrane gap by slowing the ETC reactions and by intrinsically induced electroporation that depolarizes the inner membrane. The proposed feedback mechanism is akin to a Le Chatelier's-type principle of trans-membrane potential feedback control.

为了使细胞正常工作,必须将穿过线粒体内膜的电位保持在一定范围内。提出了一种膜电位稳态的反馈控制机制,即电场的增加减少了电子传递链(ETC)的限速步骤。跨膜电场的增加通过减慢ETC反应和内在诱导的电穿孔使内膜去极化来限制质子向膜间间隙泵送的速率。所提出的反馈机制类似于跨膜电位反馈控制的勒夏特列式原理。
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引用次数: 0
Quantum features of the transport through ion channels in the soft knock-on model. 软撞击模型中离子通道输运的量子特征。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-27 DOI: 10.1088/1478-3975/ad9cde
Mateusz Polakowski, Miłosz Panfil

Ion channels are protein structures that facilitate the selective passage of ions across the membrane cells of living organisms. They are known for their high conductance and high selectivity. The precise mechanism between these two seemingly contradicting features is not yet firmly established. One possible candidate is the quantum coherence. In this work we study the quantum model of the soft knock-on conduction using the Lindblad equation taking into account the non-hermiticity of the model. We show that the model exhibits a regime in which high conductance coexists with high coherence. Our findings second the role of quantum effects in the transport properties of the ion channels.

离子通道是一种蛋白质结构,可以促进离子选择性地通过生物体的膜细胞。它们以其高电导和高选择性而闻名。这两个看似矛盾的特征之间的确切机制还没有完全确定。一个可能的候选者是量子相干性。在本文中,我们利用Lindblad方程研究了软碰撞传导的量子模型,并考虑了模型的非厄米性。我们证明了该模型呈现出高电导与高相干共存的状态。我们的发现第二是量子效应在离子通道输运特性中的作用。
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引用次数: 0
Emergence of temporal noise hierarchy in co-regulated genes of multi-output feed-forward loop. 多输出前馈回路共调基因中出现的时间噪声层次结构
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-05 DOI: 10.1088/1478-3975/ad9792
Mintu Nandi

Natural variations in gene expression, called noise, are fundamental to biological systems. The expression noise can be beneficial or detrimental to cellular functions. While the impact of noise on individual genes is well-established, our understanding of how noise behaves when multiple genes are co-expressed by shared regulatory elements within transcription networks remains elusive. This lack of understanding extends to how the architecture and regulatory features of these networks influence noise. To address this gap, we study the multi-output feed-forward loop motif. The motif is prevalent in bacteria and yeast and influences co-expression of multiple genes by shared transcription factors (TFs). Focusing on a two-output variant of the motif, the present study explores the interplay between its architecture, co-expression (symmetric and asymmetric) patterns of the two genes, and the associated noise dynamics. We employ a stochastic modeling approach to investigate how the binding affinities of the TFs influence symmetric and asymmetric expression patterns and the resulting noise dynamics in the co-expressed genes. This knowledge could guide the development of strategies for manipulating gene expression patterns through targeted modulation of TF binding affinities.

基因表达的自然变化被称为噪声,是生物系统的基本要素。表达噪音可能对细胞功能有利,也可能有害。虽然噪音对单个基因的影响已经得到证实,但我们对多个基因在转录网络中通过共享调控元件共同表达时噪音的表现仍然缺乏了解。这种认识的缺乏还延伸到了这些网络的结构和调控特征如何影响噪声。为了填补这一空白,我们研究了多输出前馈环图案。该模式普遍存在于细菌和酵母中,通过共享转录因子影响多个基因的共同表达。本研究以该图案的双输出变体为重点,探讨了其结构、两个基因的共同表达模式(包括对称和非对称表达)以及相关噪声动态之间的相互作用。我们采用随机建模的方法来研究转录因子的结合亲和力如何影响对称和非对称表达模式以及由此产生的共表达基因的噪声动态。这些知识可以指导我们制定策略,通过有针对性地调节转录因子的结合亲和力来操纵基因表达模式。
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引用次数: 0
Theory of epigenetic switching due to stochastic histone mark loss during DNA replication. DNA 复制过程中随机组蛋白标记丢失导致表观遗传学转换的理论。
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-29 DOI: 10.1088/1478-3975/ad942c
Ander Movilla Miangolarra, Martin Howard

How much information does a cell inherit from its ancestors beyond its genetic sequence? What are the epigenetic mechanisms that allow this? Despite the rise in available epigenetic data, how such information is inherited through the cell cycle is still not fully understood. Often, epigenetic marks can display bistable behaviour and their bistable state is transmitted to daughter cells through the cell cycle, providing the cell with a form of memory. However, loss-of-memory events also take place, where a daughter cell switches epigenetic state (with respect to the mother cell). Here, we develop a framework to compute these epigenetic switching rates, for the case when they are driven by DNA replication, i.e. the frequency of loss-of-memory events due to replication. We consider the dynamics of histone modifications during the cell cycle deterministically, except at DNA replication, where nucleosomes are randomly distributed between the two daughter DNA strands, which is therefore implemented stochastically. This hybrid stochastic-deterministic approach enables an analytic derivation of the replication-driven switching rate. While retaining great simplicity, this framework can explain experimental switching rate data, establishing its biological importance as a framework to quantitatively study epigenetic inheritance.

除了基因序列,细胞还能从祖先那里继承多少信息?有哪些表观遗传机制可以做到这一点?尽管现有的表观遗传学数据不断增加,但人们对这些信息如何在细胞周期中遗传仍不完全清楚。通常情况下,表观遗传标记会表现出双稳态行为,其双稳态状态会通过细胞周期传递给子细胞,为细胞提供一种记忆形式。然而,也会发生失忆事件,即子细胞(相对于母细胞)改变表观遗传状态。在此,我们开发了一个框架,用于计算这些表观遗传学切换率,即由 DNA 复制驱动的表观遗传学切换率,也就是由复制导致的失忆事件的频率。我们以确定的方式考虑组蛋白修饰在细胞周期中的动态变化,但 DNA 复制时除外,此时核小体在两条子 DNA 链之间随机分布,因此我们以随机的方式实现组蛋白修饰的动态变化。这种随机-确定混合方法可以分析推导出复制驱动的转换率。这个框架非常简单,却能解释实验中的切换率数据,从而确立了它作为定量研究表观遗传框架的生物学重要性。
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引用次数: 0
A role of fear on diseased food web model with multiple functional response. 恐惧对具有多重功能反应的病态食物网模型的作用
IF 2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-26 DOI: 10.1088/1478-3975/ad9261
Thangavel Megala, Manickasundaram Siva Pradeep, Mehmet Yavuz, Thangaraj Nandha Gopal, Muthuradhinam Sivabalan

In this paper, we analyze the role of fear in a three-species non-delayed ecological model that examines the interactions among susceptible prey, infectious (diseased) prey, and predators within a food web. The prey population grows in a logistic manner until it achieves a carrying capacity, reflecting common population dynamics in the absence of predators. Diseased prey is assumed to transmit infection to healthful prey by the use of a Holling type II reaction. Predators, alternatively, are modeled to consume their prey using Beddington-DeAngelis and Crowley-Martin response features. This evaluation specializes in ensuring the non-negativity of solutions, practical constraints on population dynamics, and long-term stability of the system. Each biologically possible equilibrium point is tested to understand the environmental stable states. Local stability is assessed through eigenvalue analysis, while global stability of positive equilibria is evaluated by the use of Lyapunov features to determine the overall stability of the model. Furthermore, Hopf bifurcation is explored primarily based on infection rateɛ. Numerical simulations are carried out to validate the theoretical effects and offer practical insights into the model behaviour under specific conditions.

本文分析了恐惧在一个三物种非延迟生态模型中的作用,该模型研究了食物网中易感猎物、传染性(患病)猎物和捕食者之间的相互作用。猎物种群以逻辑方式增长,直到达到承载能力,这反映了在没有捕食者的情况下常见的种群动态。假定患病猎物会通过霍林 II 型反应将感染传给健康猎物。捕食者则利用贝丁顿-德安吉利斯和克劳利-马丁反应特征来消耗猎物。这种评估方法专门用于确保解的非负性、对种群动态的实际限制以及系统的长期稳定性。对每个生物学上可能的平衡点进行测试,以了解环境稳定状态。局部稳定性通过特征值分析进行评估,而正平衡的全局稳定性则通过使用 Lyapunov 特征进行评估,以确定模型的整体稳定性。此外,还主要根据感染率 $varepsilon$ 探索了霍普夫分岔。我们还进行了数值模拟,以验证理论效果,并为特定条件下的模型行为提供实用见解。
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引用次数: 0
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Physical biology
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