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Exploring the interaction of myricetin with human alpha-2-macroglobulin: biophysical and in-silico analysis 探索杨梅素与人α -2巨球蛋白的相互作用:生物物理和计算机分析
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2023-01-20 DOI: 10.1007/s10867-022-09621-z
Sana Ansari, Haseeb Ahsan, Mohammad Khalid Zia, Mansour K. Gatasheh, Fahim H. Khan

Myricetin (MYR) is a bioactive secondary metabolite found in plants that is recognized for its nutraceutical value and is an essential constituent of various foods and beverages. It is reported to exhibit a plethora of activities, including antioxidant, antimicrobial, antidiabetic, anticancer, and anti-inflammatory. Alpha-2-macroglobulin (α2M) is a major plasma anti-proteinase that can inhibit proteinases of both human and non-human origin, regardless of their specificity and catalytic mechanism. Here, we explored the interaction of MYR-α2M using various biochemical and biophysical techniques. It was found that the interaction of MYR brings subtle change in its anti-proteolytic potential and thereby alters its structure and function, as can be seen from absorbance and fluorescence spectroscopy. UV spectroscopy of α2M in presence of MYR indicated the occurrence of hyperchromism, suggesting complex formation. Fluorescence spectroscopy reveals that MYR reduces the fluorescence intensity of native α2M with a shift in the wavelength maxima. At 318.15 K, MYR binds to α2M with a binding constant of 2.4 × 103 M−1, which indicates significant binding. The ΔG value was found to be − 7.56 kcal mol−1 at 298.15 K, suggesting the interaction to be spontaneous and thermodynamically favorable. The secondary structure of α2M does not involve any major change as was confirmed by CD analysis. The molecular docking indicates that Asp-146, Ser-172, Glu-174, and Tyr-180 were the key residues involved in α2M-MYR complex formation. This study contributes to our understanding of the function and mechanism of protein and flavonoid binding by providing a molecular basis of the interaction between MYR and α2M.

杨梅素(Myricetin, MYR)是一种在植物中发现的具有生物活性的次生代谢物,因其营养价值而被公认,是各种食品和饮料的基本成分。据报道,它具有多种活性,包括抗氧化、抗菌、抗糖尿病、抗癌和抗炎。α -2-巨球蛋白(α2M)是一种主要的血浆抗蛋白酶,无论其特异性和催化机制如何,都能抑制人类和非人类来源的蛋白酶。在这里,我们利用各种生化和生物物理技术探索了MYR-α2M的相互作用。从吸光度和荧光光谱可以看出,MYR的相互作用使其抗蛋白水解电位发生了微妙的变化,从而改变了其结构和功能。在MYR存在下,α - 2m的紫外光谱显示出了高显色现象,表明形成了复合物。荧光光谱分析表明,MYR降低了天然α2M的荧光强度,最大波长发生偏移。在318.15 K时,MYR与α2M结合,结合常数为2.4 × 103 M−1,表明MYR与α2M结合显著。在298.15 K时,ΔG值为−7.56 kcal mol−1,表明相互作用是自发的,热力学上有利。CD分析证实α2M的二级结构没有发生大的变化。分子对接表明Asp-146、Ser-172、Glu-174和tir -180是参与α2M-MYR复合物形成的关键残基。本研究为MYR与α2M相互作用提供了分子基础,有助于我们进一步了解蛋白与类黄酮结合的功能和机制。
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引用次数: 3
Determinant factors for residence time of kinesin motors at microtubule ends 微管末端驱动电机停留时间的决定因素
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2023-01-16 DOI: 10.1007/s10867-022-09623-x
Ping Xie

Kinesins constitute a superfamily of microtubule (MT)-based motor proteins, which can perform diverse biological functions in cells such as transporting vesicle, regulating MT dynamics, and segregating chromosome. Some motors such as kinesin-1, kinesin-2, and kinesin-3 do the activity mainly on the MT lattice, while others such as kinesin-7 and kinesin-8 do the activity mainly at the MT plus end. To perform the different functions, it is required that the former motors can reside on the MT lattice for longer times than at the end, while the latter motors can reside at the MT plus end for long times. Here, a simple but general theory of the MT-end residence time of the kinesin motor is presented, with which the factors dictating the residence time are determined. The theory is further used to study specifically the MT-end residence times of Drosophila kinesin-1, kinesin-2/KIF3AB, kinesin-3/Unc104, kinesin-5/Eg5, kinesin-7/CENP-E, and kinesin-8/Kip3 motors, with the theoretical results being in agreement with the available experimental data.

运动蛋白是一个基于微管(MT)的运动蛋白超家族,在细胞中具有转运囊泡、调节MT动力学和染色体分离等多种生物学功能。一些马达,如kinesin-1、kinesin-2和kinesin-3主要在MT晶格上进行活性,而其他马达,如kinesin-7和kinesin-8主要在MT +端进行活性。为了实现不同的功能,要求前者电机在MT晶格上驻留的时间比末端长,而后者电机在MT +端驻留的时间比末端长。本文提出了一种简单而通用的运动马达mt -末端停留时间理论,并据此确定了决定停留时间的因素。该理论进一步应用于果蝇kinesin-1、kinesin-2/KIF3AB、kinesin-3/Unc104、kinesin-5/Eg5、kinesin-7/CENP-E和kinesin-8/Kip3马达的mt -末端停留时间的具体研究,理论结果与现有实验数据一致。
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引用次数: 0
Energy-guided synapse coupling between neurons under noise 噪声下神经元间能量引导突触耦合
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2023-01-14 DOI: 10.1007/s10867-022-09622-y
Bo Hou, Jun Ma, Feifei Yang

From a physical viewpoint, any external stimuli including noise disturbance can inject energy into the media, and the electric response is regulated by the equivalent electric stimulus. For example, mode transition in electric activities in neurons occurs and kinds of spatial patterns are formed during the wave propagation. In this paper, a feasible criterion is suggested to explain and control the growth of electric synapse and memristive synapse between Hindmarsh-Rose neurons in the presence of noise. It is claimed that synaptic coupling can be enhanced adaptively due to energy diversity, and the coupling intensity is increased to a saturation value until two neurons reach certain energy balance. Two identical neurons can reach perfect synchronization when electric synapse coupling is further increased. This scheme is also considered in a chain neural network and uniform noise is applied on all neurons. However, reaching synchronization becomes difficult for neurons in presenting spiking, bursting, and chaotic and periodic patterns, even when the local energy balance is corrupted to continue further growth of the coupling intensity. In the presence of noise, energy diversity becomes uncertain because of spatial diversity in excitability, and development of regular patterns is blocked. The similar scheme is used to control the growth of memristive synapse for neurons, and the synchronization stability and pattern formation are controlled by the energy diversity among neurons effectively. These results provide possible guidance for knowing the biophysical mechanism for synapse growth and energy flow can be applied to control the synchronous patterns between neurons.

从物理角度看,包括噪声干扰在内的任何外界刺激都可以向介质注入能量,电响应受等效电刺激的调节。例如,神经元的电活动发生模式转换,电波在传播过程中形成各种空间模式。本文提出了一种可行的解释和控制噪声存在下Hindmarsh-Rose神经元间电突触和记忆突触生长的判据。由于能量的多样性,突触耦合可以自适应增强,耦合强度增加到一个饱和值,直到两个神经元达到一定的能量平衡。当电突触耦合进一步增加时,两个相同的神经元可以达到完全同步。在链式神经网络中也考虑了该方案,并对所有神经元施加均匀噪声。然而,即使局部能量平衡被破坏以继续耦合强度的进一步增长,神经元在呈现尖峰、爆裂、混沌和周期性模式时也难以达到同步。在噪声存在的情况下,由于兴奋性的空间分异,能量分异变得不确定,规则模式的发展受到阻碍。采用类似的方法控制神经元记忆突触的生长,有效地利用神经元间的能量多样性控制同步稳定性和模式形成。这些结果为了解突触生长的生物物理机制提供了可能的指导,能量流动可以用于控制神经元之间的同步模式。
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引用次数: 4
Computational analysis of synergism in small networks with different logic 不同逻辑下小网络协同效应的计算分析
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-12-29 DOI: 10.1007/s10867-022-09620-0
Menghan Chen, Ruiqi Wang

Cell fate decision processes are regulated by networks which contain different molecules and interactions. Different network topologies may exhibit synergistic or antagonistic effects on cellular functions. Here, we analyze six most common small networks with regulatory logic AND or OR, trying to clarify the relationship between network topologies and synergism (or antagonism) related to cell fate decisions. We systematically examine the contribution of both network topologies and regulatory logic to the cell fate synergism by bifurcation and combinatorial perturbation analysis. Initially, under a single set of parameters, the synergism of three types of networks with AND and OR logic is compared. Furthermore, to consider whether these results depend on the choices of parameter values, statistics on the synergism of five hundred parameter sets is performed. It is shown that the results are not sensitive to parameter variations, indicating that the synergy or antagonism mainly depends on the network topologies rather than the choices of parameter values. The results indicate that the topology with “Dual Inhibition” shows good synergism, while the topology with “Dual Promotion” or “Hybrid” shows antagonism. The results presented here may help us to design synergistic networks based on network structure and regulation combinations, which has promising implications for cell fate decisions and drug combinations.

细胞命运的决定过程是由包含不同分子和相互作用的网络调控的。不同的网络拓扑结构可能对细胞功能表现出协同或拮抗作用。在这里,我们分析了六个最常见的具有与或调控逻辑的小网络,试图澄清网络拓扑结构与与细胞命运决定相关的协同(或拮抗)之间的关系。我们通过分岔和组合摄动分析系统地研究了网络拓扑结构和调控逻辑对细胞命运协同作用的贡献。首先,在一组参数下,比较了三种具有与或逻辑的网络的协同作用。此外,为了考虑这些结果是否取决于参数值的选择,对500个参数集的协同作用进行了统计。结果表明,网络的协同或对抗主要取决于网络的拓扑结构,而不是参数值的选择。结果表明,“双抑制”拓扑具有较好的协同作用,而“双促进”或“混合”拓扑具有拮抗作用。本文提出的结果可能有助于我们设计基于网络结构和调控组合的协同网络,这对细胞命运决定和药物组合具有重要意义。
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引用次数: 0
Clinical effects of 2-DG drug restraining SARS-CoV-2 infection: A fractional order optimal control study 2-DG药物抑制SARS-CoV-2感染的临床效果:分数阶最优对照研究
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-12-02 DOI: 10.1007/s10867-022-09617-9
Piu Samui, Jayanta Mondal, Bashir Ahmad, Amar Nath Chatterjee

Fractional calculus is very convenient tool in modeling of an emergent infectious disease system comprising previous disease states, memory of disease patterns, profile of genetic variation etc. Significant complex behaviors of a disease system could be calibrated in a proficient manner through fractional order derivatives making the disease system more realistic than integer order model. In this study, a fractional order differential equation model is developed in micro level to gain perceptions regarding the effects of host immunological memory in dynamics of SARS-CoV-2 infection. Additionally, the possible optimal control of the infection with the help of an antiviral drug, viz. 2-DG, has been exemplified here. The fractional order optimal control would enable to employ the proper administration of the drug minimizing its systematic cost which will assist the health policy makers in generating better therapeutic measures against SARS-CoV-2 infection. Numerical simulations have advantages to visualize the dynamical effects of the immunological memory and optimal control inputs in the epidemic system.

分数阶微积分是一种非常方便的工具,可以用来模拟突发传染病系统,该系统包括以前的疾病状态、疾病模式记忆、遗传变异谱等。通过分数阶导数可以熟练地校准疾病系统的重要复杂行为,使疾病系统比整数阶模型更真实。在本研究中,建立了微观水平的分数阶微分方程模型,以了解宿主免疫记忆在SARS-CoV-2感染动力学中的作用。此外,在抗病毒药物(即2-DG)的帮助下,对感染的可能的最佳控制已在这里举例说明。分数阶最优控制将使适当的药物管理最小化其系统成本,这将有助于卫生政策制定者制定更好的治疗SARS-CoV-2感染的措施。数值模拟有利于可视化疫情系统中免疫记忆和最优控制输入的动态效应。
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引用次数: 3
Functionalization and Haemolytic analysis of pure superparamagnetic magnetite nanoparticle for hyperthermia application 用于热疗的纯超顺磁性纳米磁铁矿的功能化和溶血分析
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-11-25 DOI: 10.1007/s10867-022-09614-y
Hemalatha Kothandaraman, Alamelumangai Kaliyamoorthy, Arulmozhi Rajaram, Chandunika R. Kalaiselvan, Niroj Kumar Sahu, Parthipan Govindasamy, Muralidharan Rajaram

Superparamagnetic iron oxide nanoparticles (SPIONPs) are widely used in clinical research. The single domain nanoparticles are used in magnetic fluid hyperthermia (MFH) to treat cancer. When nanoparticles are exposed to an external magnetic field, it generates heat destroying tumour cells. SPIONPs have a large surface area, so the particles tend to aggregate, which leads to the destabilization of the colloidal system. To enhance the stability and biocompatibility of the nanomaterials, it is necessary to coat the surface with biocompatible material. Magnetite (Fe3O4) is a superparamagnetic nanoparticle (SPNPs) that was functionalized with oleic acid (OA) by sol–gel process using ethanol as the solvent. The oleic acid-coated magnetite (OA-Fe3O4) was characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), UV–Visible diffuse reflectance spectroscopy (UV-DRS) and vibrating sample magnetometer (VSM). The haemolysis test has been used to investigate the haemocompatibility properties of nanomaterials. Hyperthermia study shows a high SAR value for the concentration of 1 mg/ml at the field of 600 Oe and frequency of 316 kHz. The OA coating enhanced the haemocompatibility of synthesized magnetite nanoparticles which can be used for magnetic fluid hyperthermia applications.

超顺磁性氧化铁纳米颗粒(SPIONPs)广泛应用于临床研究。单畴纳米颗粒用于磁流体热疗(MFH)治疗癌症。当纳米颗粒暴露在外部磁场中时,它会产生热量,摧毁肿瘤细胞。SPIONPs具有较大的表面积,因此粒子容易聚集,从而导致胶体系统的不稳定。为了提高纳米材料的稳定性和生物相容性,有必要在纳米材料表面涂覆生物相容性材料。磁铁矿(Fe3O4)是一种超顺磁性纳米粒子(SPNPs),以乙醇为溶剂,采用溶胶-凝胶法与油酸(OA)进行了功能化处理。采用x射线粉末衍射(XRD)、傅里叶红外光谱(FTIR)、透射电子显微镜(TEM)、热重分析(TGA)、紫外-可见漫反射光谱(UV-DRS)和振动样品磁强计(VSM)对油酸包覆磁铁矿(OA-Fe3O4)进行了表征。溶血试验已被用于研究纳米材料的血液相容性。热疗研究表明,浓度为1 mg/ml时,在600 Oe场和316khz频率下具有较高的SAR值。OA涂层增强了合成的磁铁矿纳米颗粒的血液相容性,可用于磁流体热疗应用。
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引用次数: 0
Computational and comparative investigation of hydrophobic profile of spike protein of SARS-CoV-2 and SARS-CoV SARS-CoV-2和SARS-CoV刺突蛋白疏水性谱的计算和比较研究
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-11-23 DOI: 10.1007/s10867-022-09615-x
Uma Shekhawat, Anindita Roy Chowdhury (Chakravarty)

The hydrophobic force is one of the most dominant factors in protein folding. A protein becomes functional only when it achieves its three-dimensional structure and stability upon folding. For a better understanding of the hydrophobic effects and their function in protein folding, quantitative measurement of the hydrophobicity of amino acid side chains is crucial. Spike protein is the primary structural protein in SARS-CoV-2 and SARS-CoV. This study explores how protein sequences in SARS-CoV-2 and SARS-CoV spike proteins encode hydrophobic interactions. Computational tools/techniques have been utilized to investigate the protein sequences of the spike proteins of SARS-CoV-2 and SARS-CoV. Investigations provided an estimate of hydrophobic distribution and its relative strength, indicating a hydrophobic pattern. Analysis of the spike protein's hydrophobic profile may help identify and treat the virus-caused disease; additionally, it can give an insight into the transmissibility and pathogenicity of the virus.

疏水力是蛋白质折叠中最主要的因素之一。只有当蛋白质在折叠时达到其三维结构和稳定性时,它才具有功能。为了更好地了解蛋白质折叠中的疏水效应及其功能,氨基酸侧链疏水性的定量测量至关重要。刺突蛋白是SARS-CoV-2和SARS-CoV的主要结构蛋白。本研究探讨了SARS-CoV-2和SARS-CoV刺突蛋白中的蛋白质序列如何编码疏水相互作用。利用计算工具/技术研究了SARS-CoV-2和SARS-CoV刺突蛋白的蛋白质序列。研究提供了疏水分布及其相对强度的估计,表明疏水模式。对刺突蛋白疏水性谱的分析可能有助于识别和治疗病毒引起的疾病;此外,它可以深入了解病毒的传播性和致病性。
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引用次数: 2
A pilot study of ion current estimation by ANN from action potential waveforms 基于动作电位波形的人工神经网络估计离子电流的初步研究
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-11-14 DOI: 10.1007/s10867-022-09619-7
Sevgi Şengül Ayan, Selim Süleymanoğlu, Hasan Özdoğan

Experiments using conventional experimental approaches to capture the dynamics of ion channels are not always feasible, and even when possible and feasible, some can be time-consuming. In this work, the ionic current–time dynamics during cardiac action potentials (APs) are predicted from a single AP waveform by means of artificial neural networks (ANNs). The data collection is accomplished by the use of a single-cell model to run electrophysiological simulations in order to identify ionic currents based on fluctuations in ion channel conductance. The relevant ionic currents, as well as the corresponding cardiac AP, are then calculated and fed into the ANN algorithm, which predicts the desired currents solely based on the AP curve. The validity of the proposed methodology for the Bayesian approach is demonstrated by the R (validation) scores obtained from training data, test data, and the entire data set. The Bayesian regularization’s (BR) strength and dependability are further supported by error values and the regression presentations, all of which are positive indicators. As a result of the high convergence between the simulated currents and the currents generated by including the efficacy of a developed Bayesian solver, it is possible to generate behavior of ionic currents during time for the desired AP waveform for any electrical excitable cell.

使用传统的实验方法来捕获离子通道动力学的实验并不总是可行的,即使在可能和可行的情况下,有些也可能是耗时的。在这项工作中,利用人工神经网络(ann)从单个心脏动作电位(APs)波形预测了心脏动作电位(APs)期间的离子电流时间动力学。数据收集是通过使用单细胞模型来运行电生理模拟来完成的,以便根据离子通道电导的波动来识别离子电流。然后计算相关的离子电流,以及相应的心脏AP,并将其输入到人工神经网络算法中,该算法仅根据AP曲线预测所需的电流。贝叶斯方法的有效性通过从训练数据、测试数据和整个数据集获得的R(验证)分数来证明。误差值和回归表示进一步支持了贝叶斯正则化(BR)的强度和可靠性,它们都是积极的指标。由于模拟电流和包括开发的贝叶斯求解器的有效性所产生的电流之间的高度收敛,因此可以为任何电可激细胞生成所需AP波形期间的离子电流行为。
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引用次数: 0
Correction to: Non-extensitivity and criticality of atomic hydropathicity around a voltage-gated sodium channel’s pore: a modeling study 修正:电压门控钠通道孔周围原子亲水性的非广泛性和临界性:模型研究
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-11-12 DOI: 10.1007/s10867-022-09616-w
Markos N. Xenakis, Dimos Kapetis, Yang Yang, Jordi Heijman, Stephen G. Waxman, Giuseppe Lauria, Catharina G. Faber, Hubert J. Smeets, Patrick J. Lindsey, Ronald L. Westra
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引用次数: 0
A dynamical model of combination therapy applied to glioma 胶质瘤联合治疗的动力学模型
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2022-11-11 DOI: 10.1007/s10867-022-09618-8
Handoko Handoko, Setyanto Tri Wahyudi, Ardian Arif Setyawan, Agus Kartono

Glioma is a human brain tumor that is very difficult to treat at an advanced stage. Studies of glioma biomarkers have shown that some markers are released into the bloodstream, so data from these markers indicate a decrease in the concentration of blood glucose and serum glucose in patients with glioma; these suggest an association between glucose and glioma. This decrease mechanism in glucose concentration can be described by the coupled ordinary differential equations of the early-stage glioma growth and interactions between glioma cells, immune cells, and glucose concentration. In this paper, we propose developing a new mathematical model to explain how glioma cells evolve and survive combination therapy between chemotherapy and oncolytic virotherapy, as an alternative to glioma treatment. In this study, three therapies were applied for analysis, that is, (1) chemotherapy, (2) virotherapy, and (3) a combination of chemotherapy and virotherapy. Virotherapy uses specialist viruses that only attack tumor cells. Based on the simulation results of the therapy carried out, we conclude that combination therapy can reduce the glioma cells significantly compared to the other two therapies. The simulation results of this combination therapy can be an alternative to glioma therapy.

神经胶质瘤是一种人类脑肿瘤,在晚期很难治疗。对神经胶质瘤生物标志物的研究表明,一些标志物被释放到血液中,因此这些标志物的数据表明,神经胶质瘤患者的血糖和血清葡萄糖浓度下降;这表明葡萄糖和神经胶质瘤之间存在关联。这种葡萄糖浓度下降的机制可以用早期胶质瘤生长和胶质瘤细胞、免疫细胞和葡萄糖浓度相互作用的耦合常微分方程来描述。在本文中,我们提出建立一个新的数学模型来解释胶质瘤细胞如何进化和生存的化疗和溶瘤病毒治疗的联合治疗,作为胶质瘤治疗的替代方案。本研究采用三种治疗方法进行分析,即(1)化疗,(2)病毒治疗,(3)化疗与病毒治疗联合。病毒疗法使用专门的病毒,只攻击肿瘤细胞。根据所进行治疗的模拟结果,我们得出结论,与其他两种治疗相比,联合治疗可以显著减少胶质瘤细胞。这种联合治疗的模拟结果可以替代胶质瘤治疗。
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引用次数: 0
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