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An overview of Helium-3 NMR: Recent developments and applications 氦-3核磁共振综述:最近的发展和应用
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-08-01 DOI: 10.1016/j.pnmrs.2023.08.001
Leonid B. Krivdin

The present review is focused on experimental and theoretical methods together with applications of helium NMR in chemistry and biochemistry. It comprises two main sections, the first dealing with standardization and instrumentation for 3He NMR spectroscopy and the second dealing with its practical applications, mainly those in general and organic chemistry with a special emphasis on the rapidly developing and exciting area of fullerenes encapsulating helium atoms. Several general applications of 3He NMR spectroscopy in physical chemistry and biomedicine are also briefly discussed.

综述了氦核磁共振的实验方法和理论方法,以及它在化学和生物化学中的应用。它包括两个主要部分,第一部分涉及3He核磁共振光谱的标准化和仪器仪表,第二部分涉及其实际应用,主要是一般和有机化学中的应用,特别强调快速发展和令人兴奋的富勒烯封装氦原子的领域。并简要讨论了3He核磁共振波谱在物理化学和生物医学中的几种一般应用。
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引用次数: 0
Implementation and applications of shaped pulses in EPR 成形脉冲在EPR中的实现与应用
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-08-01 DOI: 10.1016/j.pnmrs.2023.04.003
Burkhard Endeward, Matthias Bretschneider, Paul Trenkler, Thomas F. Prisner

In this review, we describe the application of shaped pulses for EPR spectroscopy. Pulses generated by fast arbitrary waveform generators are mostly used in the field of EPR spectroscopy for broadband (200 MHz-1 GHz) excitation of paramagnetic species. The implementation and optimization of such broadband pulses in existing EPR spectrometers, often designed and optimized for short rectangular microwave pulses, is demanding. Therefore, a major part of this review will describe in detail the implementation, testing and optimization of shaped pulses in existing EPR spectrometers. Additionally, we review applications using such pulses for broadband inversion of longitudinal magnetization as well as for the creation and manipulation of transverse magnetization in the field of dipolar and hyperfine EPR spectroscopy. They demonstrate the great potential of shaped pulses to improve the performance of pulsed EPR experiments. We give a brief theoretical description of shaped pulses and their limitations, especially for adiabatic pulses, most often used in EPR. We believe that this review can on the one hand be of practical use to EPR groups starting to work with such pulses, and on the other hand give readers an overview of the state of the art of shaped pulse applications in EPR spectroscopy.

本文综述了形状脉冲在EPR光谱中的应用。快速任意波形发生器产生的脉冲主要用于EPR光谱领域的宽带(200 MHz-1 GHz)顺磁物质激励。现有的EPR光谱仪通常是为短矩形微波脉冲设计和优化的,因此对这种宽带脉冲的实现和优化要求很高。因此,本综述的主要部分将详细介绍在现有EPR光谱仪上实现、测试和优化形状脉冲。此外,我们回顾了这些脉冲在纵向磁化的宽带反演以及在偶极和超精细EPR光谱领域中横向磁化的创建和操作的应用。它们证明了形状脉冲在提高脉冲EPR实验性能方面的巨大潜力。我们给出了形状脉冲及其局限性的简要理论描述,特别是绝热脉冲,最常用于EPR。我们相信,这篇综述一方面可以对开始使用这种脉冲的EPR小组有实际用途,另一方面可以让读者对EPR光谱学中成形脉冲应用的现状有一个概述。
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引用次数: 1
Pure shift edited NMR methodologies for the extraction of Homo- and heteronuclear couplings with ultra-high resolution 纯移位编辑核磁共振方法的提取与超高分辨率的同核和异核耦合
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-08-01 DOI: 10.1016/j.pnmrs.2023.02.001
Sandeep Kumar Mishra , N. Suryaprakash

The scalar couplings that result in the splitting of the signals in the NMR spectrum arise due to the interaction of the nuclear spins, whereby the spin polarization is transmitted through chemical bonds. The interaction strengths depend inter alia on the number of consecutive chemical bonds intervening between the two interacting spins and on the molecular conformation. The pairwise interaction of many spins in a molecule resulting in a complex spectrum poses a severe challenge to analyse the spectrum and hence the determination of magnitudes and signs of homo- and heteronuclear couplings. The problem is more severe in the analysis of 1H spectra than the spectra of most of the other nuclei due to the often very small chemical shift dispersion. As a consequence, the straightforward analysis and the accurate extraction of the coupling constants from the 1H spectrum of a complex spin system continues to remain a challenge, and often may be a formidable task. Over the years, the several pure shift-based one‐dimensional and two‐dimensional methodologies have been developed by workers in the field, which provide broadband homonuclear decoupling of proton spectra, removing the complexity but at the cost of the very informative scalar couplings. To circumvent this problem, several one‐dimensional and two‐dimensional NMR experiments have been developed for the determination of homonuclear and heteronuclear couplings (nJHX, where n = 1,2,3) while retaining the high resolution obtained by implementing pure shift strategies. This review attempts to summarize the extensive work reported by a large number of researchers over the years for the accurate determination of homo- and heteronuclear scalar couplings.

导致核磁共振谱中信号分裂的标量耦合是由于核自旋的相互作用引起的,自旋极化是通过化学键传递的。相互作用强度除其他外取决于两个相互作用自旋之间的连续化学键的数目和分子的构象。分子中许多自旋的成对相互作用导致了复杂的光谱,这对分析光谱以及确定同核和异核耦合的大小和标志提出了严峻的挑战。由于化学位移色散往往非常小,在分析1H谱时,这个问题比分析其他大多数原子核谱时更为严重。因此,从复杂自旋系统的1H谱中直接分析和准确提取耦合常数仍然是一个挑战,而且往往是一项艰巨的任务。多年来,该领域的工作者已经开发了几种纯基于位移的一维和二维方法,它们提供了质子谱的宽带同核解耦,消除了复杂性,但代价是非常信息的标量耦合。为了避免这个问题,一些一维和二维核磁共振实验已经被开发出来,用于确定同核和异核耦合(nJHX,其中n = 1,2,3),同时保持通过实施纯移位策略获得的高分辨率。这篇综述试图总结大量研究人员多年来为准确测定同核和异核标量耦合所做的大量工作。
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引用次数: 0
Affinity measurement of strong ligands with NMR spectroscopy: Limitations and ways to overcome them 核磁共振波谱法测定强配体的亲和性:局限性和克服方法
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-07-18 DOI: 10.1016/j.pnmrs.2023.07.001
Claudio Dalvit , Isabel Gmür , Philip Rößler , Alvar D. Gossert

NMR spectroscopy is currently extensively used in binding assays for hit identification, but its use in dissociation constant determination is more limited when compared to other biophysical techniques, in particular for tight binders. Although NMR is quite suitable for measuring the binding strength of weak to medium affinity ligands with dissociation constant KD > 1 μM, it has some limitations in the determination of the binding strength of tight binders (KD < 1 μM). A theoretical analysis of the binding affinity determination of strong ligands using different types of NMR experiments is provided and practical guidelines are given for overcoming the limitations and for the proper set-up of the experiments. Some approaches require reagents with unique properties or highly specialized equipment, while others can be applied quite generally. We describe all approaches in detail, but give higher emphasis to the more general methods, like competition experiments, where we include actual experimental data and discuss the practical aspects.

核磁共振波谱目前广泛应用于结合分析,用于命中鉴定,但与其他生物物理技术相比,它在解离常数测定中的应用更为有限,特别是对于紧密结合物。虽然核磁共振非常适合测量离解常数为KD >的弱至中等亲和配体的结合强度;1 μM,在确定紧密结合剂的结合强度(KD <1μM)。利用不同类型的核磁共振实验对强配体的结合亲和力测定进行了理论分析,并给出了克服这些限制和正确设置实验的实用指南。一些方法需要具有独特性质的试剂或高度专业化的设备,而另一些方法可以相当普遍地应用。我们详细描述了所有方法,但更强调更一般的方法,如竞争实验,我们包括实际的实验数据,并讨论实际方面。
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引用次数: 0
Recent technical developments and clinical research applications of sodium (23Na) MRI 钠(23Na) MRI的最新技术进展及临床研究应用
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-04-18 DOI: 10.1016/j.pnmrs.2023.04.002
Lena V. Gast , Tanja Platt , Armin M. Nagel , Teresa Gerhalter

Sodium is an essential ion that plays a central role in many physiological processes including the transmembrane electrochemical gradient and the maintenance of the body’s homeostasis. Due to the crucial role of sodium in the human body, the sodium nucleus is a promising candidate for non-invasively assessing (patho-)physiological changes. Almost 10 years ago, Madelin et al. provided a comprehensive review of methods and applications of sodium (23Na) MRI (Madelin et al., 2014) [1]. More recent review articles have focused mainly on specific applications of 23Na MRI. For example, several articles covered 23Na MRI applications for diseases such as osteoarthritis (Zbyn et al., 2016, Zaric et al., 2020) [[2], [3]], multiple sclerosis (Petracca et al., 2016, Huhn et al., 2019) [[4], [5]] and brain tumors (Schepkin, 2016) [6], or for imaging certain organs such as the kidneys (Zollner et al., 2016) [7], the brain (Shah et al., 2016, Thulborn et al., 2018) [[8], [9]], and the heart (Bottomley, 2016) [10]. Other articles have reviewed technical developments such as radiofrequency (RF) coils for 23Na MRI (Wiggins et al., 2016, Bangerter et al., 2016) [[11], [12]], pulse sequences (Konstandin et al., 2014) [13], image reconstruction methods (Chen et al., 2021) [14], and interleaved/simultaneous imaging techniques (Lopez Kolkovsky et al., 2022) [15]. In addition, 23Na MRI topics have been covered in review articles with broader topics such as multinuclear MRI or ultra-high-field MRI (Niesporek et al., 2019, Hu et al., 2019, Ladd et al., 2018) [[16], [17], [18]].

During the past decade, various research groups have continued working on technical improvements to sodium MRI and have investigated its potential to serve as a diagnostic and prognostic tool. Clinical research applications of 23Na MRI have covered a broad spectrum of diseases, mainly focusing on the brain, cartilage, and skeletal muscle (see Fig. 1). In this article, we aim to provide a comprehensive summary of methodological and hardware developments, as well as a review of various clinical research applications of sodium (23Na) MRI in the last decade (i.e., published from the beginning of 2013 to the end of 2022).

钠是一种重要的离子,在许多生理过程中起着核心作用,包括跨膜电化学梯度和维持身体的稳态。由于钠在人体中的重要作用,钠核是非侵入性评估(病理)生理变化的有希望的候选者。大约在10年前,Madelin等人对钠(23Na) MRI的方法和应用进行了全面综述(Madelin et al., 2014)[1]。最近的评论文章主要集中在23Na MRI的具体应用上。例如,有几篇文章涵盖了23Na MRI在骨关节炎(Zbyn等人,2016,Zaric等人,2020)[[2],[3]]、多发性硬化症(Petracca等人,2016,Huhn等人,2019)[[4],[5]]和脑肿瘤(Schepkin, 2016)[6]等疾病的应用,或用于肾脏(Zollner等人,2016)[7]、大脑(Shah等人,2016,Thulborn等人,2018)[[8],[9]]和心脏(Bottomley, 2016)[10]等器官的成像。其他文章回顾了技术发展,如用于23Na MRI的射频(RF)线圈(Wiggins等人,2016年,Bangerter等人,2016年)[[11],[12]],脉冲序列(Konstandin等人,2014年)[13],图像重建方法(Chen等人,2021年)[14]和交错/同步成像技术(Lopez Kolkovsky等人,2022年)[15]。此外,多核MRI或超高场MRI等更广泛主题的综述文章也涵盖了23Na MRI主题(Niesporek等人,2019,Hu等人,2019,Ladd等人,2018)[[16],[17],[18]]。在过去的十年中,不同的研究小组继续致力于钠核磁共振成像的技术改进,并研究了其作为诊断和预后工具的潜力。23Na MRI的临床研究应用涵盖了广泛的疾病,主要集中在脑、软骨和骨骼肌(见图1)。在本文中,我们旨在全面总结方法和硬件的发展,并回顾近十年来(即从2013年初到2022年底)钠(23Na) MRI的各种临床研究应用。
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引用次数: 0
Electron paramagnetic resonance spectroscopy in structural-dynamic studies of large protein complexes 电子顺磁共振波谱在大型蛋白质复合物结构动力学研究中的应用
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-04-01 DOI: 10.1016/j.pnmrs.2022.11.001
Laura Galazzo, Enrica Bordignon

Macromolecular protein assemblies are of fundamental importance for many processes inside the cell, as they perform complex functions and constitute central hubs where reactions occur. Generally, these assemblies undergo large conformational changes and cycle through different states that ultimately are connected to specific functions further regulated by additional small ligands or proteins. Unveiling the 3D structural details of these assemblies at atomic resolution, identifying the flexible parts of the complexes, and monitoring with high temporal resolution the dynamic interplay between different protein regions under physiological conditions is key to fully understanding their properties and to fostering biomedical applications.

In the last decade, we have seen remarkable advances in cryo-electron microscopy (EM) techniques, which deeply transformed our vision of structural biology, especially in the field of macromolecular assemblies. With cryo-EM, detailed 3D models of large macromolecular complexes in different conformational states became readily available at atomic resolution. Concomitantly, nuclear magnetic resonance (NMR) and electron paramagnetic resonance spectroscopy (EPR) have benefited from methodological innovations which also improved the quality of the information that can be achieved. Such enhanced sensitivity widened their applicability to macromolecular complexes in environments close to physiological conditions and opened a path towards in-cell applications.

In this review we will focus on the advantages and challenges of EPR techniques with an integrative approach towards a complete understanding of macromolecular structures and functions.

大分子蛋白质组装对细胞内的许多过程都具有重要的基础作用,因为它们执行复杂的功能并构成发生反应的中心枢纽。一般来说,这些组合经历了巨大的构象变化,并在不同的状态中循环,最终与特定的功能相连,这些功能由额外的小配体或蛋白质进一步调节。在原子分辨率下揭示这些组件的3D结构细节,识别复合物的柔性部分,并以高时间分辨率监测生理条件下不同蛋白质区域之间的动态相互作用,是充分了解其特性和促进生物医学应用的关键。在过去的十年中,低温电子显微镜(EM)技术取得了显著的进步,深刻地改变了我们对结构生物学的看法,特别是在大分子组装领域。使用低温电镜,不同构象状态的大型大分子复合物的详细三维模型在原子分辨率上变得容易获得。与此同时,核磁共振(NMR)和电子顺磁共振波谱(EPR)也受益于方法创新,这些创新也提高了可以获得的信息质量。这种增强的灵敏度扩大了它们在接近生理条件的环境中对大分子复合物的适用性,并为细胞内应用开辟了道路。在这篇综述中,我们将重点介绍EPR技术的优势和挑战,并以综合的方法全面了解大分子结构和功能。
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引用次数: 3
Identifying disease progression in chronic kidney disease using proton magnetic resonance spectroscopy 利用质子磁共振波谱识别慢性肾病的疾病进展
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-04-01 DOI: 10.1016/j.pnmrs.2023.04.001
Tyrone L.R. Humphries , David A. Vesey , Graham J. Galloway , Glenda C. Gobe , Ross S. Francis

Chronic kidney disease (CKD) affects approximately 10% of the world population, higher still in some developing countries, and can cause irreversible kidney damage eventually leading to kidney failure requiring dialysis or kidney transplantation. However, not all patients with CKD will progress to this stage, and it is difficult to distinguish between progressors and non-progressors at the time of diagnosis. Current clinical practice involves monitoring estimated glomerular filtration rate and proteinuria to assess CKD trajectory over time; however, there remains a need for novel, validated methods that differentiate CKD progressors and non-progressors. Nuclear magnetic resonance techniques, including magnetic resonance spectroscopy and magnetic resonance imaging, have the potential to improve our understanding of CKD progression. Herein, we review the application of magnetic resonance spectroscopy both in preclinical and clinical settings to improve the diagnosis and surveillance of patients with CKD.

慢性肾脏疾病(CKD)影响了大约10%的世界人口,在一些发展中国家仍然更高,并且可以导致不可逆的肾脏损害,最终导致肾衰竭,需要透析或肾移植。然而,并非所有CKD患者都会发展到这一阶段,在诊断时很难区分进展者和非进展者。目前的临床实践包括监测肾小球滤过率和蛋白尿来评估CKD的长期发展轨迹;然而,仍然需要新的、经过验证的方法来区分CKD进展者和非进展者。核磁共振技术,包括磁共振波谱和磁共振成像,有可能提高我们对CKD进展的理解。在此,我们回顾了磁共振波谱在临床前和临床环境中的应用,以提高CKD患者的诊断和监测。
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引用次数: 0
Nanoscale quantum sensing with Nitrogen-Vacancy centers in nanodiamonds – A magnetic resonance perspective 纳米金刚石中氮空位中心的纳米量子传感——磁共振视角
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-04-01 DOI: 10.1016/j.pnmrs.2022.12.001
Takuya F. Segawa , Ryuji Igarashi

Nanodiamonds containing fluorescent Nitrogen-Vacancy (NV) centers are the smallest single particles, of which a magnetic resonance spectrum can be recorded at room temperature using optically-detected magnetic resonance (ODMR). By recording spectral shift or changes in relaxation rates, various physical and chemical quantities can be measured such as the magnetic field, orientation, temperature, radical concentration, pH or even NMR. This turns NV-nanodiamonds into nanoscale quantum sensors, which can be read out by a sensitive fluorescence microscope equipped with an additional magnetic resonance upgrade. In this review, we introduce the field of ODMR spectroscopy of NV-nanodiamonds and how it can be used to sense different quantities. Thereby we highlight both, the pioneering contributions and the latest results (covered until 2021) with a focus on biological applications.

含有荧光氮空位(NV)中心的纳米金刚石是最小的单粒子,可以在室温下使用光学检测磁共振(ODMR)记录其磁共振光谱。通过记录光谱位移或弛豫速率的变化,可以测量各种物理和化学量,如磁场、取向、温度、自由基浓度、pH甚至NMR。这将NV纳米金刚石转化为纳米级量子传感器,可以通过配备额外磁共振升级的灵敏荧光显微镜读取。在这篇综述中,我们介绍了NV纳米金刚石的ODMR光谱领域,以及如何使用它来感知不同的数量。因此,我们强调了开创性的贡献和最新的成果(涵盖到2021年),重点关注生物应用。
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引用次数: 9
Metabolic imaging with deuterium labeled substrates 氘标记底物的代谢成像
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2023-04-01 DOI: 10.1016/j.pnmrs.2023.02.002
Jacob Chen Ming Low, Alan J. Wright, Friederike Hesse, Jianbo Cao, Kevin M. Brindle

Deuterium metabolic imaging (DMI) is an emerging clinically-applicable technique for the non-invasive investigation of tissue metabolism. The generally short T1 values of 2H-labeled metabolites in vivo can compensate for the relatively low sensitivity of detection by allowing rapid signal acquisition in the absence of significant signal saturation. Studies with deuterated substrates, including [6,6′-2H2]glucose, [2H3]acetate, [2H9]choline and [2,3-2H2]fumarate have demonstrated the considerable potential of DMI for imaging tissue metabolism and cell death in vivo. The technique is evaluated here in comparison with established metabolic imaging techniques, including PET measurements of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake and 13C MR imaging of the metabolism of hyperpolarized 13C-labeled substrates.

氘代谢成像(DMI)是一种新兴的临床应用技术,用于非侵入性研究组织代谢。体内2H标记代谢物的通常较短的T1值可以通过在没有显著信号饱和的情况下允许快速信号采集来补偿相对较低的检测灵敏度。对氘化底物,包括[6,6′-2H2]葡萄糖、[2H3]乙酸盐、[2H9]胆碱和[2,3-2H2]富马酸盐的研究表明,DMI在体内组织代谢和细胞死亡成像方面具有相当大的潜力。该技术在此与已建立的代谢成像技术进行比较,包括2-脱氧-2-[18F]氟-d-葡萄糖(FDG)摄取的PET测量和超极化13C-标记底物代谢的13C-MR成像。
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引用次数: 5
In-cell NMR: Why and how? 细胞内核磁共振:为什么?如何?
IF 6.1 2区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2022-10-01 DOI: 10.1016/j.pnmrs.2022.04.002
Francois-Xavier Theillet , Enrico Luchinat

NMR spectroscopy has been applied to cells and tissues analysis since its beginnings, as early as 1950. We have attempted to gather here in a didactic fashion the broad diversity of data and ideas that emerged from NMR investigations on living cells. Covering a large proportion of the periodic table, NMR spectroscopy permits scrutiny of a great variety of atomic nuclei in all living organisms non-invasively. It has thus provided quantitative information on cellular atoms and their chemical environment, dynamics, or interactions. We will show that NMR studies have generated valuable knowledge on a vast array of cellular molecules and events, from water, salts, metabolites, cell walls, proteins, nucleic acids, drugs and drug targets, to pH, redox equilibria and chemical reactions. The characterization of such a multitude of objects at the atomic scale has thus shaped our mental representation of cellular life at multiple levels, together with major techniques like mass-spectrometry or microscopies.

NMR studies on cells has accompanied the developments of MRI and metabolomics, and various subfields have flourished, coined with appealing names: fluxomics, foodomics, MRI and MRS (i.e. imaging and localized spectroscopy of living tissues, respectively), whole-cell NMR, on-cell ligand-based NMR, systems NMR, cellular structural biology, in-cell NMR… All these have not grown separately, but rather by reinforcing each other like a braided trunk. Hence, we try here to provide an analytical account of a large ensemble of intricately linked approaches, whose integration has been and will be key to their success.

We present extensive overviews, firstly on the various types of information provided by NMR in a cellular environment (the “why”, oriented towards a broad readership), and secondly on the employed NMR techniques and setups (the “how”, where we discuss the past, current and future methods). Each subsection is constructed as a historical anthology, showing how the intrinsic properties of NMR spectroscopy and its developments structured the accessible knowledge on cellular phenomena. Using this systematic approach, we sought i) to make this review accessible to the broadest audience and ii) to highlight some early techniques that may find renewed interest. Finally, we present a brief discussion on what may be potential and desirable developments in the context of integrative studies in biology.

早在1950年,核磁共振光谱学就开始应用于细胞和组织分析。我们试图在这里以一种说教的方式收集从核磁共振对活细胞的研究中产生的广泛多样的数据和想法。核磁共振光谱学覆盖了元素周期表的很大一部分,允许对所有生物体中各种各样的原子核进行无创检查。因此,它提供了细胞原子及其化学环境、动力学或相互作用的定量信息。我们将展示核磁共振研究已经产生了关于大量细胞分子和事件的宝贵知识,从水、盐、代谢物、细胞壁、蛋白质、核酸、药物和药物靶点,到pH值、氧化还原平衡和化学反应。在原子尺度上对如此众多的物体进行表征,从而形成了我们在多个层面上对细胞生命的心理表征,以及质谱法或显微镜等主要技术。核磁共振对细胞的研究伴随着核磁共振和代谢组学的发展,各个子领域蓬勃发展,创造了吸引人的名字:通量组学,食物组学,MRI和MRS(分别是活组织的成像和定位光谱),全细胞核磁共振,基于细胞配体的核磁共振,系统核磁共振,细胞结构生物学,细胞内核磁共振……所有这些都不是分开发展的,而是像编织的树干一样相互加强。因此,我们试图在这里提供一种对错综复杂的方法的大集合的分析说明,这些方法的集成已经并且将是它们成功的关键。我们提供了广泛的概述,首先是核磁共振在细胞环境中提供的各种类型的信息(“为什么”,面向广泛的读者),其次是所采用的核磁共振技术和设置(“如何”,我们讨论过去,现在和未来的方法)。每个小节都是作为一个历史选集构建的,展示了核磁共振波谱的内在特性及其发展如何构建了细胞现象的可访问知识。使用这种系统的方法,我们寻求i)使这篇综述能够被最广泛的受众所接受,ii)突出一些可能重新引起兴趣的早期技术。最后,我们简要讨论了在生物学综合研究的背景下可能存在的潜在和可取的发展。
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引用次数: 17
期刊
Progress in Nuclear Magnetic Resonance Spectroscopy
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