A major goal in structural biology is to unravel how molecular machines function in detail. To that end, solution-state NMR spectroscopy is ideally suited as it is able to study biological assemblies in a near natural environment. Based on methyl TROSY methods, it is now possible to record high-quality data on complexes that are far over 100 kDa in molecular weight. In this review, we discuss the theoretical background of methyl TROSY spectroscopy, the information that can be extracted from methyl TROSY spectra and approaches that can be used to assign methyl resonances in large complexes. In addition, we touch upon insights that have been obtained for a number of challenging biological systems, including the 20S proteasome, the RNA exosome, molecular chaperones and G-protein-coupled receptors. We anticipate that methyl TROSY methods will be increasingly important in modern structural biology approaches, where information regarding static structures is complemented with insights into conformational changes and dynamic intermolecular interactions. NMR spectroscopy is a versatile tool for studying time-dependent processes chemical reactions, phase transitions or macromolecular structure changes. However, time-resolved NMR is usually based on the simplest among available techniques - one-dimensional spectra serving as "snapshots" of the studied process. One of the reasons is that multidimensional experiments are very time-expensive due to costly sampling of evolution time space. In this review we summarize efforts to alleviate the problem of limited applicability of multidimensional NMR in time-resolved studies. We focus on techniques based on sparse or non-uniform sampling (NUS), which lead to experimental time reduction by omitting a significant part of the data during measurement and reconstructing it mathematically, adopting certain assumptions about the spectrum. NUS spectra are faster to acquire than conventional ones and thus better suited to the role of "snapshots", but still suffer from non-stationarity of the signal i.e. amplitude and frequency variations within a dataset. We discuss in detail how these instabilities affect the spectra, and what are the optimal ways of sampling the non-stationary FID signal. Finally, we discuss related areas of NMR where serial experiments are exploited and how they can benefit from the same NUS-based approaches. The blood-brain barrier (BBB) regulates the transfer of solutes and essential nutrients into the brain. Growing evidence supports BBB dysfunction in a range of acute and chronic brain diseases, justifying the need for novel research and clinical tools that can non-invasively detect, characterize, and quantify BBB dysfunction in-vivo. Many approaches already exist for measuring BBB dysfunction in man using positron emission tomography and magnetic resonance imaging (e.g. dynamic contrast-enhanced MRI measurements of gadolinium leakage). This review paper focusses on MRI measurements of water exchange across the BBB, which occurs through a wide range of pathways, and is likely to be a highly sensitive marker of BBB dysfunction. Key mathematical models and acquisition methods are discussed for the two main approaches those that utilize contrast agents to enhance relaxation rate differences between the intravascular and extravascular compartments and so enhance the sensitivity of MRI signals to BBB water exchange, and those that utilize the dynamic properties of arterial spin labelling to first isolate signal from intravascular spins and then estimate the impact of water exchange on the evolving signal. Data from studies in healthy and pathological brain tissue are discussed, in addition to validation studies in rodents. Crown V. All rights reserved.Dynamical NMR spectroscopy provides unique mechanistic understanding of the transport and relaxation processes in glass-forming liquids over timescales typically ranging from ~10-9 s to ~102 s, and thus has been used extensively in the past to study the dynamical behavior of polymeric and organic glass-forming liquids. However, reports in the literature of similar studies on inorganic glass-forming liquids have remained somewhat limited due to the experimental challenges.  https://www.selleckchem.com/products/cinchocaine.html  In this contribution we present a review of the high-temperature NMR spectroscopic studies of atomic and molecular dynamics in a wide variety of inorganic glass-forming liquids including oxides, halides and chalcogenides as well as select ionic liquids and molten salts. The significance of these dynamical processes in understanding the nature of the liquid-to-glass transition and their connection with the macroscopic transport properties of these liquids are discussed. The analysis of mixtures by NMR spectroscopy is challenging. Diffusion-ordered NMR spectroscopy enables a pseudo-separation of species based on differences in their translational diffusion coefficients. Under the right circumstances, this is a powerful technique; however, when molecules diffuse at similar rates separation in the diffusion dimension can be poor. In addition, spectral overlap also limits resolution and can make interpretation challenging. Matrix-assisted diffusion NMR seeks to improve resolution in the diffusion dimension by utilising the differential interaction of components in the mixture with an additive to the solvent. Tuning these matrix-analyte interactions allows the diffusion resolution to be optimised. This review presents the background to matrix-assisted diffusion experiments, surveys the wide range of matrices employed, including chromatographic stationary phases, surfactants and polymers, and demonstrates the current state of the art. Airway epithelium is the first body surface to contact inhaled irritants and report danger. Here, we report how epithelial cells recognize and respond to aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp., because proteases are critical components of many allergens that provoke asthma. In a murine model, Alp1 elicits helper T (Th) cell-dependent lung eosinophilia that is initiated by the rapid response of bronchiolar club cells to Alp1. Alp1 damages bronchiolar cell junctions, which triggers a calcium flux signaled through calcineurin within club cells of the bronchioles, inciting inflammation. In two human cohorts, we link fungal sensitization and/or asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 is also necessary and sufficient for club cells to sensitize mice to Alp1. Thus, club cells detect junction damage as mechanical stress, which signals danger via TRPV4, calcium, and calcineurin to initiate allergic sensitization.