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Generation of cellular reactive oxygen and nitrogen species by exposure to ultraviolet radiation. 暴露于紫外线辐射下细胞活性氧和活性氮的产生。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-14 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01298-7
Macarena Menoni, Pablo Alcoba, María J Zuluaga, R Daniel Peluffo

Reactive oxygen and nitrogen species, such as superoxide and peroxynitrite anions, are produced in our body as a result of normal metabolic functions or under pathologic conditions (oxidative and nitro-oxidative stress). A well-documented battery of antioxidant enzymes and cofactors are in place to fight this stress and restore the redox balance of the cell. However, comprehensive information on the generation of these reactive species by exposing cell components to ultraviolet (UV) light, specifically UVA and UVB sunlight, is scarce or missing. In this short review, we attempt to cover several enzymes and cofactors that are targets of UV radiation as it relates to the production (or consumption) of these oxidants, and, when known, discuss the underlying mechanisms. Because of their key importance, UV light effects on DNA are briefly discussed.

活性氧和活性氮,如超氧和过氧亚硝酸盐阴离子,在我们体内作为正常代谢功能或病理条件(氧化和氮氧化应激)的结果产生。一组有充分证据的抗氧化酶和辅助因子可以对抗这种压力,恢复细胞的氧化还原平衡。然而,关于细胞成分暴露于紫外线(UV)光,特别是UVA和UVB阳光下产生这些活性物质的全面信息很少或缺失。在这篇简短的综述中,我们试图涵盖几种与这些氧化剂的产生(或消耗)有关的紫外线辐射目标酶和辅助因子,并在已知时讨论其潜在机制。鉴于它们的重要意义,本文简要讨论了紫外光对DNA的影响。
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引用次数: 0
Liquid‒liquid phase separation and poly(ADP‒ribosyl)ation in the context of ultraviolet radiation-induced stress in mammalian cells. 哺乳动物细胞在紫外线诱导应激下的液-液相分离和聚(adp -核糖基)化。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-11 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01294-x
Daniela Mejías, Valentina Seballos, Laura Lafon-Hughes

Poly(ADP‒ribose) polymerases (PARPs) consume NAD+ to synthesize poly(ADP‒ribose) (PAR) primarily via post-translational modification. PAR is degraded mainly by poly (ADP-ribose) glycohydrolase (PARG). PAR can be linear or branched and can have up to 200 monomers. With two phosphates per monomer, PAR is highly negatively charged. PAR can be recognized by specific protein domains and has been described as a "glue" or scaffold for the assembly of multiprotein complexes. PAR is involved in several diverse cellular structures and functions, including DNA replication, transcription, DNA repair, chromatin structure and imprinting regulation, mitotic spindle assembly, cell‒cell junctions, cytoplasmic granule formation, biomineralization and the formation of pathological aggregates. Here, we review the effects of ultraviolet radiation (UVR) on mammalian cells, emphasizing the participation of PAR metabolism in the novel paradigm of liquid‒liquid phase separation (LLPS). Further studies demand interdisciplinary approaches, undoubtedly requiring contributions from biophysicists.

Supplementary information: The online version contains supplementary material available at 10.1007/s12551-025-01294-x.

聚(adp -核糖)聚合酶(PARPs)主要通过翻译后修饰来消耗NAD+合成聚(adp -核糖)(PAR)。PAR主要由聚(adp -核糖)糖水解酶(PARG)降解。PAR可以是线性的,也可以是支链的,最多可以有200个单体。由于每个单体有两个磷酸,PAR带高度负电荷。PAR可以被特定的蛋白质结构域识别,并被描述为多蛋白质复合物组装的“胶水”或支架。PAR参与多种不同的细胞结构和功能,包括DNA复制、转录、DNA修复、染色质结构和印迹调节、有丝分裂纺锤体组装、细胞-细胞连接、细胞质颗粒形成、生物矿化和病理聚集体的形成。在这里,我们回顾了紫外线辐射(UVR)对哺乳动物细胞的影响,强调了PAR代谢在液-液相分离(LLPS)新范式中的参与。进一步的研究需要跨学科的方法,无疑需要生物物理学家的贡献。补充信息:在线版本包含补充资料,提供地址为10.1007/s12551-025-01294-x。
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引用次数: 0
Biophysics of SARS-CoV-2 spike protein's receptor-binding domain interaction with ACE2 and neutralizing antibodies: from computation to functional insights. SARS-CoV-2刺突蛋白受体结合域与ACE2和中和抗体相互作用的生物物理学:从计算到功能见解
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-08 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01276-z
Fernando Luís Barroso da Silva, Karen Paco, Aatto Laaksonen, Animesh Ray

The spike protein encoded by the SARS-CoV-2 has become one of the most studied macromolecules in recent years due to its central role in COVID-19 pathogenesis. The spike protein's receptor-binding domain (RBD) directly interacts with the host-encoded receptor protein, ACE2. This review critically examines computational insights into RBD's interaction with ACE2 and with therapeutic antibodies designed to interfere with this interaction. We begin by summarizing insights from early computational studies on pre-pandemic SARS-CoV-1 RBD interactions and how these early studies shaped the understanding of SARS-CoV-2. Next, we highlight key theoretical contributions that revealed the molecular mechanisms behind the binding affinity of SARS-CoV-2 RBD against ACE2, and the structural changes that have enhanced the infectivity of emerging variants. Special attention is given to the "RBD charge rule", a predictive framework for determining variant infectivity based on the electrostatic properties of the RBD. Towards applying the computational insights to therapy, we discuss a multiscale computational protocol for optimizing monoclonal antibodies to improve binding affinity across multiple spike protein variants, including representatives from the Omicron family. Finally, we explore how these insights can inform the development of future vaccines and therapeutic interventions for combating future coronavirus diseases.

SARS-CoV-2编码的刺突蛋白因其在COVID-19发病机制中的核心作用而成为近年来研究最多的大分子之一。刺突蛋白的受体结合域(RBD)直接与宿主编码的受体蛋白ACE2相互作用。这篇综述批判性地研究了RBD与ACE2相互作用的计算见解,以及设计用于干扰这种相互作用的治疗性抗体。我们首先总结了SARS-CoV-1大流行前RBD相互作用的早期计算研究的见解,以及这些早期研究如何塑造了对SARS-CoV-2的理解。接下来,我们重点介绍了揭示SARS-CoV-2 RBD与ACE2结合亲和力背后的分子机制以及增强新变体传染性的结构变化的关键理论贡献。特别注意的是“RBD电荷规则”,这是一种基于RBD静电特性确定变异感染性的预测框架。为了将计算见解应用于治疗,我们讨论了优化单克隆抗体的多尺度计算方案,以提高多个刺突蛋白变体的结合亲和力,包括来自Omicron家族的代表。最后,我们探讨了这些见解如何为未来疫苗和治疗干预措施的开发提供信息,以对抗未来的冠状病毒疾病。
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引用次数: 0
New therapeutic strategies for malaria. 疟疾的新治疗策略。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-08 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01296-9
Alessandro Sá Pinheiro, Patricia Rieken Macedo Rocco, Celso Caruso-Neves, Ana Acacia Sá Pinheiro

Malaria is a life-threatening parasitic disease and remains a significant global health problem, associated with high morbidity and mortality. Malaria cases are widely spread, but the highest incidence occurs in tropical and subtropical areas, especially in developing countries. Despite all efforts to control the disease, the number of cases increased by 5 million from 2021 to 2022. The mechanisms of malaria pathogenesis are still not fully understood. This, combined with the parasite's recurrent ability to develop resistance to standard treatments, hinders effective disease management and control. Therefore, a deep understanding of parasite biology, along with the various aspects of host-parasite interactions, is essential for malaria elimination. Extracellular vesicles (EVs) are membrane-enclosed vesicles which are secreted by a variety of cells. These tiny structures have emerged as a key component in the mechanisms of pathogenesis of different parasitic diseases, promoting cell-to-cell communication, even in distance. In this review, we explore the latest advancements in EV research in the malaria field, focusing on their role in pathophysiology, as well as their potential as diagnostic tools, alternative therapeutic strategies, and vaccine development. We conclude by highlighting key elements in EV research that could provide insights into the translational application of EVs.

疟疾是一种危及生命的寄生虫病,仍然是一个重大的全球健康问题,与高发病率和高死亡率有关。疟疾病例广泛传播,但最高发病率发生在热带和亚热带地区,特别是在发展中国家。尽管为控制该疾病做出了各种努力,但从2021年到2022年,病例数增加了500万。疟疾的发病机制尚不完全清楚。这一点,再加上寄生虫对标准治疗产生耐药性的复发能力,阻碍了有效的疾病管理和控制。因此,深入了解寄生虫生物学,以及宿主-寄生虫相互作用的各个方面,对于消除疟疾至关重要。细胞外囊泡(EVs)是由多种细胞分泌的膜封闭囊泡。这些微小结构已成为不同寄生虫病发病机制的关键组成部分,促进细胞间的通信,甚至是远距离通信。在这篇综述中,我们探讨了EV在疟疾领域的最新研究进展,重点关注它们在病理生理学中的作用,以及它们在诊断工具、替代治疗策略和疫苗开发方面的潜力。最后,我们强调了电动汽车研究中的关键因素,这些因素可以为电动汽车的转化应用提供见解。
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引用次数: 0
Fluorescence phasor analysis: basic principles and biophysical applications. 荧光相量分析:基本原理及其生物物理应用。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-07 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01293-y
Alvaro A Recoulat Angelini, Leonel Malacrida, F Luis González Flecha

Fluorescence is one of the most widely used techniques in biological sciences. Its exceptional sensitivity and versatility make it a tool of first choice for quantitative studies in biophysics. The concept of phasors, originally introduced by Charles Steinmetz in the late nineteenth century for analyzing alternating current circuits, has since found applications across diverse disciplines, including fluorescence spectroscopy. The main idea behind fluorescence phasors was posited by Gregorio Weber in 1981. By analyzing the complementary nature of pulse and phase fluorometry data, he shows that two magnitudes-denoted as G and S-derived from the frequency-domain fluorescence measurements correspond to the real and imaginary parts of the Fourier transform of the fluorescence intensity in the time domain. This review provides a historical perspective on how the concept of phasors originates and how it integrates into fluorescence spectroscopy. We discuss their fundamental algebraic properties, which enable intuitive model-free analysis of fluorescence data despite the complexity of the underlying phenomena. Some applications in molecular biophysics illustrate the power of this approach in studying diverse phenomena, including protein folding, protein interactions, phase transitions in lipid mixtures, and formation of high-order structures in nucleic acids.

荧光技术是生物科学中应用最广泛的技术之一。其卓越的灵敏度和多功能性使其成为生物物理学定量研究的首选工具。相量的概念最初是由查尔斯·斯坦梅茨(Charles Steinmetz)在19世纪末提出的,用于分析交流电路,此后在包括荧光光谱学在内的各个学科中得到了应用。荧光相量背后的主要思想是由格雷戈里奥·韦伯在1981年提出的。通过分析脉冲和相位荧光测量数据的互补性,他表明,从频域荧光测量中得出的两个幅度(表示为G和s)对应于荧光强度在时域的傅里叶变换的实部和虚部。本文综述了相量概念的起源及其与荧光光谱学的结合。我们讨论了它们的基本代数性质,尽管潜在现象的复杂性,但它们能够对荧光数据进行直观的无模型分析。分子生物物理学中的一些应用说明了这种方法在研究各种现象方面的力量,包括蛋白质折叠、蛋白质相互作用、脂质混合物中的相变和核酸中高阶结构的形成。
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引用次数: 0
RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance. 假单胞菌门的RND/HAE-1成员:探索多药耐药性。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-07 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01297-8
Vinnícius Machado Schelk Gomes, Ana Carolina Silva Bulla, Pedro Henrique Monteiro Torres, Manuela Leal da Silva

The hydrophobe/amphiphile efflux-1 (HAE-1) family, part of the Resistance-Nodulation-Division (RND) superfamily, plays a critical role in the development of multidrug resistance (MDR) in bacteria. Known for its broad substrate transport capacity, this family of efflux pumps can actively expel a wide range of molecules, including antibiotics, salts, and dyes, thereby reducing the intracellular concentration of toxic substances. These transporters, which form efflux systems, are primarily found in bacteria within the phylum Pseudomonadota (Proteobacteria), where they are strongly associated with increased resistance and enhanced virulence, thus contributing to bacterial survival in hostile environments. In addition, efflux systems are composed of two other protein components: Membrane Fusion Proteins (MFPs) and Outer Membrane Factors (OMFs). Notably, several bacterial species identified by the World Health Organization (WHO) as urgent priorities for new antibiotic development, such as Escherichia coli and Pseudomonas aeruginosa, have well-studied HAE-1 efflux systems, such as AcrAB-TolC and MexAB-OprM. These systems efficiently transport molecules from the periplasm to the extracellular space, facilitating bacterial persistence. In this review, we examined the current knowledge of HAE-1 efflux transporters and their roles in the physiology and survival of bacteria in the Pseudomonadota phylum.

疏水/两亲外排-1 (HAE-1)家族是耐药-结瘤-分裂(RND)超家族的一部分,在细菌多药耐药(MDR)的发展中起着至关重要的作用。该外排泵家族以其广泛的底物运输能力而闻名,可以主动排出各种分子,包括抗生素、盐和染料,从而降低细胞内有毒物质的浓度。这些形成外排系统的转运蛋白主要存在于假单胞菌门(变形菌门)内的细菌中,它们与增强的耐药性和增强的毒力密切相关,从而有助于细菌在恶劣环境中的生存。此外,外排系统由另外两种蛋白质成分组成:膜融合蛋白(MFPs)和外膜因子(OMFs)。值得注意的是,一些被世界卫生组织(WHO)确定为新抗生素开发的紧急优先事项的细菌物种,如大肠杆菌和铜绿假单胞菌,已经充分研究了HAE-1外排系统,如AcrAB-TolC和MexAB-OprM。这些系统有效地将分子从周质转运到细胞外空间,促进细菌的生存。在这篇综述中,我们研究了目前关于HAE-1外排转运体的知识及其在假单胞菌门细菌的生理和生存中的作用。
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引用次数: 0
Chirality transfer to nanocrystals by peptide templates and circularly polarized light. 手性转移到纳米晶体的肽模板和圆偏振光。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-07 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01278-x
Marcelo Yudi Icimoto, Vitor Oliveira, Iseli Lourenço Nantes

Since the early advent of nanotechnology, proteins, peptides, and amino acids have frequently been used to synthesize and stabilize metallic and ceramic nanoparticles. Also, several signaling peptides and enzymes have the activity modulated by the association with nanostructured particles and films. Lately, with the discovery of giant magnetoresistance and chiral-induced spin selectivity, an innovative nanotechnological use of amino acids and proteins emerged. Enantiomeric pairs of amino acids, peptides, and other biomolecules have been used as templates for growing chiral distorted nanocrystals and for chiral functionalization of achiral nanoparticles. More recently, circularly polarized light has been raised as an alternative for synthesizing enantiomeric pairs of plasmonic nanocrystals on anisotropic seeds. These chiral nanostructured materials exhibit unique properties with applications in biological and technological fields harnessed in various applications, including biosensing, asymmetric catalysis, and optical devices. This review presents the experimental strategies and mechanisms of chirality transfer to plasmonic and ceramic nanoparticles using peptide templates and circularly polarized light.

自从纳米技术出现以来,蛋白质、多肽和氨基酸经常被用来合成和稳定金属和陶瓷纳米粒子。此外,一些信号肽和酶的活性通过与纳米结构颗粒和膜的结合而调节。最近,随着巨磁电阻和手性诱导自旋选择性的发现,氨基酸和蛋白质的创新纳米技术出现了。氨基酸对映体、多肽和其他生物分子已被用作生长手性扭曲纳米晶体和非手性纳米颗粒手性功能化的模板。最近,圆偏振光已被提出作为在各向异性种子上合成等离子体纳米晶体对映体对的替代方法。这些手性纳米结构材料在生物和技术领域具有独特的应用特性,包括生物传感、不对称催化和光学器件。本文综述了利用肽模板和圆偏振光将手性转移到等离子体纳米粒子和陶瓷纳米粒子上的实验策略和机制。
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引用次数: 0
Physical communication pathways in bacteria: an extra layer to quorum sensing. 细菌的物理通信途径:群体感应的额外层。
IF 4.9 Q1 BIOPHYSICS Pub Date : 2025-03-04 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01290-1
Virgilio de la Viuda, Javier Buceta, Iago Grobas

Bacterial communication is essential for survival, adaptation, and collective behavior. While chemical signaling, such as quorum sensing, has been extensively studied, physical cues play a significant role in bacterial interactions. This review explores the diverse range of physical stimuli, including mechanical forces, electromagnetic fields, temperature, acoustic vibrations, and light that bacteria may experience with their environment and within a community. By integrating these diverse communication pathways, bacteria can coordinate their activities and adapt to changing environmental conditions. Furthermore, we discuss how these physical stimuli modulate bacterial growth, lifestyle, motility, and biofilm formation. By understanding the underlying mechanisms, we can develop innovative strategies to combat bacterial infections and optimize industrial processes.

细菌的交流对生存、适应和集体行为至关重要。虽然诸如群体感应等化学信号已被广泛研究,但物理信号在细菌相互作用中起着重要作用。这篇综述探讨了各种物理刺激的范围,包括机械力、电磁场、温度、声波振动和光,细菌可能在其环境和群落内经历。通过整合这些不同的通信途径,细菌可以协调它们的活动并适应不断变化的环境条件。此外,我们讨论了这些物理刺激如何调节细菌的生长、生活方式、运动和生物膜的形成。通过了解潜在的机制,我们可以制定创新的策略来对抗细菌感染和优化工业流程。
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引用次数: 0
Structural determinants of soft memory in recurrent biological networks. 循环生物网络中软记忆的结构决定因素。
IF 4.9 Q1 BIOPHYSICS Pub Date : 2025-03-03 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01295-w
Maria Sol Vidal-Saez, Jordi Garcia-Ojalvo

Recurrent neural networks are frequently studied in terms of their information-processing capabilities. The structural properties of these networks are seldom considered, beyond those emerging from the connectivity tuning necessary for network training. However, real biological networks have non-contingent architectures that have been shaped by evolution over eons, constrained partly by information-processing criteria, but more generally by fitness maximization requirements. Here, we examine the topological properties of existing biological networks, focusing in particular on gene regulatory networks in bacteria. We identify structural features, both local and global, that dictate the ability of recurrent networks to store information on the fly and process complex time-dependent inputs.

递归神经网络在信息处理能力方面经常被研究。除了网络训练所需的连接性调优之外,这些网络的结构特性很少被考虑。然而,真正的生物网络具有非偶然的架构,这些架构是由千万年的进化形成的,部分受到信息处理标准的限制,但更普遍的是受到适应性最大化要求的限制。在这里,我们研究了现有生物网络的拓扑特性,特别关注细菌中的基因调控网络。我们确定了局部和全局的结构特征,这些结构特征决定了循环网络在飞行中存储信息和处理复杂的时间依赖输入的能力。
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引用次数: 0
Magnesium sulfate in oxidative stress-associated pathologies: clinical, cellular, and molecular perspectives. 硫酸镁在氧化应激相关病理:临床,细胞和分子的观点。
IF 3.7 Q1 BIOPHYSICS Pub Date : 2025-03-01 eCollection Date: 2025-04-01 DOI: 10.1007/s12551-025-01292-z
Reinaldo Marín, Cilia Abad, Deliana Rojas, Miguel Fernández, Fernando Ruette

Magnesium sulfate (MgSO₄) is a therapeutically versatile agent used across various medical conditions. This review integrates experimental and computational findings to elucidate the clinical, cellular, molecular, and electronic mechanisms underlying MgSO₄'s therapeutic effects, focusing on its antioxidant properties. MgSO₄ remains the gold standard treatment for preeclampsia and eclampsia, preventing seizures and mitigating oxidative damage. In preterm birth, it offers fetal neuroprotection, although its efficacy as a tocolytic agent is limited. MgSO₄ also shows promise in treating respiratory conditions, notably severe asthma, where it acts as a bronchodilator. Its applications extend to anesthesia, pain management, and cardiac arrhythmias, reflecting its diverse pharmacological actions. Advanced computational methods, including molecular dynamics simulations and quantum chemistry calculations, have revealed how MgSO₄ interacts with cell membranes and neutralizes hydroxyl radicals. These studies suggest that MgSO₄'s antioxidant effects stem from its ability to stabilize membrane structures and modulate electron transfer processes. The therapeutic effects are mediated through multiple pathways, including calcium channel modulation, NMDA receptor antagonism, and anti-inflammatory mechanisms. Although generally safe, MgSO₄ requires careful monitoring due to its narrow therapeutic window. Future research should focus on precision dosing strategies, innovative delivery systems, and expanded therapeutic applications. A comprehensive understanding of MgSO₄'s molecular mechanisms and clinical applications will further optimize its therapeutic use.

Graphical abstract:

硫酸镁(MgSO₄)是一种治疗用途广泛的药物,用于各种医疗条件。本文综合了实验和计算结果,阐明了硫酸镁治疗效果的临床、细胞、分子和电子机制,重点是其抗氧化性能。硫酸镁仍然是治疗先兆子痫和子痫的金标准,可以预防癫痫发作并减轻氧化损伤。在早产,它提供胎儿神经保护,虽然它的功效作为一个溶胎剂是有限的。硫酸镁也显示出治疗呼吸系统疾病的希望,特别是严重哮喘,它可以作为支气管扩张剂。它的应用扩展到麻醉、疼痛管理和心律失常,反映了它的多种药理作用。先进的计算方法,包括分子动力学模拟和量子化学计算,揭示了硫酸镁如何与细胞膜相互作用并中和羟基自由基。这些研究表明,硫酸镁的抗氧化作用源于其稳定膜结构和调节电子转移过程的能力。治疗效果是通过多种途径介导的,包括钙通道调节、NMDA受体拮抗和抗炎机制。虽然mgso4通常是安全的,但由于其狭窄的治疗窗口,需要仔细监测。未来的研究应侧重于精确给药策略、创新给药系统和扩大治疗应用。全面了解硫酸镁的分子机制和临床应用将进一步优化其治疗应用。图形化的简介:
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引用次数: 0
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