-
1.
MR imaging and spectroscopy in degenerative ataxias: toward multimodal, multisite, multistage monitoring of neurodegeneration.
Öz, G, Harding, IH, Krahe, J, Reetz, K
Current opinion in neurology. 2020;(4):451-461
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW Degenerative ataxias are rare and currently untreatable movement disorders, primarily characterized by neurodegeneration in the cerebellum and brainstem. We highlight MRI studies with the most potential for utility in pending ataxia trials and underscore advances in disease characterization and diagnostics in the field. RECENT FINDINGS With availability of advanced MRI acquisition methods and specialized software dedicated to the analysis of MRI of the cerebellum, patterns of cerebellar atrophy in different degenerative ataxias are increasingly well defined. The field further embraced rigorous multimodal investigations to study network-level microstructural and functional brain changes and their neurochemical correlates. MRI and magnetic resonance spectroscopy were shown to be more sensitive to disease progression than clinical scales and to detect abnormalities in premanifest mutation carriers. SUMMARY Magnetic resonance techniques are increasingly well placed for characterizing the expression and progression of degenerative ataxias. The most impactful work has arguably come through multi-institutional studies that monitor relatively large cohorts, multimodal investigations that assess the sensitivity of different measures and their interrelationships, and novel imaging approaches that are targeted to known pathophysiology (e.g., iron and spinal imaging in Friedreich ataxia). These multimodal, multi-institutional studies are paving the way to clinical trial readiness and enhanced understanding of disease in degenerative ataxias.
-
2.
Do nuclear magnetic resonance (NMR)-based metabolomics improve the prediction of pregnancy-related disorders? Findings from a UK birth cohort with independent validation.
McBride, N, Yousefi, P, White, SL, Poston, L, Farrar, D, Sattar, N, Nelson, SM, Wright, J, Mason, D, Suderman, M, et al
BMC medicine. 2020;(1):366
Abstract
BACKGROUND Prediction of pregnancy-related disorders is usually done based on established and easily measured risk factors. Recent advances in metabolomics may provide earlier and more accurate prediction of women at risk of pregnancy-related disorders. METHODS We used data collected from women in the Born in Bradford (BiB; n = 8212) and UK Pregnancies Better Eating and Activity Trial (UPBEAT; n = 859) studies to create and validate prediction models for pregnancy-related disorders. These were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small for gestational age (SGA), large for gestational age (LGA) and preterm birth (PTB). We used ten-fold cross-validation and penalised regression to create prediction models. We compared the predictive performance of (1) risk factors (maternal age, pregnancy smoking, body mass index (BMI), ethnicity and parity) to (2) nuclear magnetic resonance-derived metabolites (N = 156 quantified metabolites, collected at 24-28 weeks gestation) and (3) combined risk factors and metabolites. The multi-ethnic BiB cohort was used for training and testing the models, with independent validation conducted in UPBEAT, a multi-ethnic study of obese pregnant women. RESULTS Maternal age, pregnancy smoking, BMI, ethnicity and parity were retained in the combined risk factor and metabolite models for all outcomes apart from PTB, which did not include maternal age. In addition, 147, 33, 96, 51 and 14 of the 156 metabolite traits were retained in the combined risk factor and metabolite model for GDM, HDP, SGA, LGA and PTB, respectively. These include cholesterol and triglycerides in very low-density lipoproteins (VLDL) in the models predicting GDM, HDP, SGA and LGA, and monounsaturated fatty acids (MUFA), ratios of MUFA to omega 3 fatty acids and total fatty acids, and a ratio of apolipoprotein B to apolipoprotein A-1 (APOA:APOB1) were retained predictors for GDM and LGA. In BiB, discrimination for GDM, HDP, LGA and SGA was improved in the combined risk factors and metabolites models. Risk factor area under the curve (AUC 95% confidence interval (CI)): GDM (0.69 (0.64, 0.73)), HDP (0.74 (0.70, 0.78)) and LGA (0.71 (0.66, 0.75)), and SGA (0.59 (0.56, 0.63)). Combined risk factor and metabolite models AUC 95% (CI): GDM (0.78 (0.74, 0.81)), HDP (0.76 (0.73, 0.79)) and LGA (0.75 (0.70, 0.79)), and SGA (0.66 (0.63, 0.70)). For GDM, HDP and LGA, but not SGA, calibration was good for a combined risk factor and metabolite model. Prediction of PTB was poor for all models. Independent validation in UPBEAT at 24-28 weeks and 15-18 weeks gestation confirmed similar patterns of results, but AUCs were attenuated. CONCLUSIONS Our results suggest a combined risk factor and metabolite model improves prediction of GDM, HDP and LGA, and SGA, when compared to risk factors alone. They also highlight the difficulty of predicting PTB, with all models performing poorly.
-
3.
NMR spectroscopy: a powerful tool for the analysis of polyphenols in extra virgin olive oil.
Olmo-Cunillera, A, López-Yerena, A, Lozano-Castellón, J, Tresserra-Rimbau, A, Vallverdú-Queralt, A, Pérez, M
Journal of the science of food and agriculture. 2020;(5):1842-1851
Abstract
Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has aroused interest in recent years due to its health properties. Nuclear magnetic resonance (NMR) spectroscopy is an appropriate tool for the accurate quantification of minor compounds in complex food matrices, such as polyphenols in olive oil. Flavonoids, lignans, secoiridoids and phenolic acids and alcohols in EVOO have been identified and quantified by NMR. This review provides an overview of the major developments in the structural elucidation of polyphenol compounds in EVOO. © 2019 Society of Chemical Industry.
-
4.
Microbial growth rates and local external mass transfer coefficients in a porous bed biofilm system measured by 19 F magnetic resonance imaging of structure, oxygen concentration, and flow velocity.
Simkins, JW, Stewart, PS, Codd, SL, Seymour, JD
Biotechnology and bioengineering. 2020;(5):1458-1469
Abstract
19 F nuclear magnetic resonance (NMR) oximetry and 1 H NMR velocimetry were used to noninvasively map oxygen concentrations and hydrodynamics in space and time in a model packed bed biofilm system in the presence and absence of flow. The development of a local oxygen sink associated with a single gel bead inoculated with respiring Escherichia coli was analyzed with a phenomenological model to determine the specific growth rate of the bacteria in situ, returning a value (0.66 hr-1 ) that was close to that measured independently in planktonic culture (0.62 hr-1 ). The decay of oxygen concentration in and around the microbiologically active bead was delayed and slower in experiments conducted under continuous flow in comparison to no-flow experiments. Concentration boundary layer thicknesses were determined and Sherwood numbers calculated to quantify external mass transfer resistance. Boundary layers were thicker in no-flow experiments compared to experiments with flow. Whereas the oxygen concentration profile across a reactive biofilm particle was symmetric in no-flow experiments, it was asymmetric with respect to flow direction in flow experiments with Sherwood numbers on the leading edge (Sh = 7) being larger than the trailing edge (Sh = 3.5). The magnitude of the experimental Sh was comparable to values predicted by a variety of correlations. These spatially resolved measurements of oxygen distribution in a geometrically complex model reveal in innovative detail the local coupling between microbial growth, oxygen consumption, and external mass transfer.
-
5.
Molecular Details of a Salt Bridge and Its Role in Insulin Fibrillation by NMR and Raman Spectroscopic Analysis.
Ratha, BN, Kar, RK, Bednarikova, Z, Gazova, Z, Kotler, SA, Raha, S, De, S, Maiti, NC, Bhunia, A
The journal of physical chemistry. B. 2020;(7):1125-1136
Abstract
Insulin, a simple polypeptide hormone with huge biological importance, has long been known to self-assemble in vitro and form amyloid-like fibrillar aggregates. Utilizing high-resolution NMR, Raman spectroscopy, and computational analysis, we demonstrate that the fluctuation of the carboxyl terminal (C-ter) residues of the insulin B-chain plays a key role in the growth phase of insulin aggregation. By comparing the insulin sourced from bovine, human, and the modified glargine (GI), we observed reduced aggregation propensity in the GI variant, resulting from two additional Arg residues at its C-ter. NMR analysis showed atomic contacts and residue-specific interactions, particularly the salt bridge and H-bond formed among the C-ter residues Arg31B, Lys29B, and Glu4A. These inter-residue interactions were reflected in strong nuclear Overhauser effects among Arg31BδH-Glu4AδH and Lys29BδHs-Glu4AδH in GI, as well as the associated downfield chemical shift of several A-chain amino terminal (N-ter) residues. The two additional Arg residues of GI, Arg31B and Arg32B, enhanced the stability of the GI native structure by strengthening the Arg31B, Lys29B, and Glu4A salt bridge, thus reducing extensive thermal distortion and fluctuation of the terminal residues. The high stability of the salt bridge retards tertiary collapse, a crucial biochemical event for oligomerization and subsequent fibril formation. Circular dichroism and Raman spectroscopic measurement also suggest slow structural distortion in the early phase of the aggregation of GI because of the restricted mobility of the C-ter residues as explained by NMR. In addition, the structural and dynamic parameters derived from molecular dynamics simulations of insulin variants highlight the role of residue-specific contacts in aggregation and amyloid-like fibril formation.
-
6.
Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment.
da Eira Silva, V, Painelli, VS, Shinjo, SK, Ribeiro Pereira, W, Cilli, EM, Sale, C, Gualano, B, Otaduy, MC, Artioli, GG
Scientific reports. 2020;(1):4908
Abstract
Carnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alternative to quantify carnosine in human skeletal muscle. However, carnosine quantification by 1H-MRS has some potential limitations that warrant a thorough experimental examination of its validity. The present investigation examined the reliability, accuracy and sensitivity for the determination of muscle carnosine in humans using in vitro and in vivo experiments and comparing it to reference method for carnosine quantification (high-performance liquid chromatography - HPLC). We used in vitro 1H-MRS to verify signal linearity and possible noise sources. Carnosine was determined in the m. gastrocnemius by 1H-MRS and HPLC to compare signal quality and convergent validity. 1H-MRS showed adequate discriminant validity, but limited reliability and poor agreement with a reference method. Low signal amplitude, low signal-to-noise ratio, and voxel repositioning are major sources of error.
-
7.
Characterization of Carbonic Anhydrase In Vivo Using Magnetic Resonance Spectroscopy.
Tomar, JS, Shen, J
International journal of molecular sciences. 2020;(7)
Abstract
Carbonic anhydrase is a ubiquitous metalloenzyme that catalyzes the reversible interconversion of CO2/HCO3-. Equilibrium of these species is maintained by the action of carbonic anhydrase. Recent advances in magnetic resonance spectroscopy have allowed, for the first time, in vivo characterization of carbonic anhydrase in the human brain. In this article, we review the theories and techniques of in vivo 13C magnetization (saturation) transfer magnetic resonance spectroscopy as they are applied to measuring the rate of exchange between CO2 and HCO3- catalyzed by carbonic anhydrase. Inhibitors of carbonic anhydrase have a wide range of therapeutic applications. Role of carbonic anhydrases and their inhibitors in many diseases are also reviewed to illustrate future applications of in vivo carbonic anhydrase assessment by magnetic resonance spectroscopy.
-
8.
Magnetic Resonance Spectroscopy of the Head and Neck: Principles, Applications, and Challenges.
Fujima, N, Carlota Andreu-Arasa, V, Barest, GD, Srinivasan, A, Sakai, O
Neuroimaging clinics of North America. 2020;(3):283-293
Abstract
Several investigations have revealed the utility of magnetic resonance spectroscopy (MRS) as an adjunct in the evaluation of lesions of the head and neck. This technique remains a challenge in the head and neck because of its low signal-to-noise ratio and long acquisition times. In this review article, the basics of image acquisition technique and reported clinical utilities of head and neck MRS are presented.
-
9.
NMR Metabolomics Applied on the Discrimination of Variables Influencing Tomato (Solanum lycopersicum).
Abreu, AC, Fernández, I
Molecules (Basel, Switzerland). 2020;(16)
Abstract
Tomato composition and nutritional value are attracting increasing attention and interest from both consumers and producers. The interest in enhancing fruits' quality with respect to beneficious nutrients and flavor/aroma components is based not only in their economic added value but also in their implications involving organoleptic and healthy properties and has generated considerable research interest among nutraceutical and horticultural industries. The present article reviews up to March 2020 some of the most relevant studies based on the application of NMR coupled to multivariate statistical analysis that have addressed the investigation on tomato (Solanum lycopersicum). Specifically, the NMR untargeted technique in the agri-food sector can generate comprehensive data on metabolic networks and is paving the way towards the understanding of variables affecting tomato crops and composition such as origin, variety, salt-water irrigation, cultivation techniques, stage of development, among many others. Such knowledge is helpful to improve fruit quality through cultural practices that divert the metabolism towards the desired pathways and, probably more importantly, drives further efforts towards the differentiation of those crops developed under controlled and desired agronomical conditions.
-
10.
Recent directions in the solid-state NMR study of synthetic and natural calcium phosphates.
Gervais, C, Bonhomme, C, Laurencin, D
Solid state nuclear magnetic resonance. 2020;:101663
Abstract
Materials containing a calcium phosphate component have been the subject of much interest to NMR spectroscopists, especially in view of understanding the structure and properties of mineralized tissues like bone and teeth, and of developing synthetic biomaterials for bone regeneration. Here, we present a selection of recent developments in their structural characterization using advanced solid state NMR experiments, highlighting the level of insight which can now be accessed.