High-resolution, liquid state nuclear magnetic resonance (NMR) spectroscopy is a popular platform for metabolic profiling because the technique is nondestructive, quantitative, reproducible, and the spectra contain a wealth of biochemical information. Because of the large dynamic range of metabolite concentrations in biofluids, statistical analyses of one-dimensional (1D) proton NMR data tend to be biased toward selecting changes in more abundant metabolites. Although two-dimensional (2D) proton-proton experiments can alleviate spectral crowding, they have been mainly used for structural determination. In this study, 2D total correlation spectroscopy NMR was used to compare the global metabolic profiles of urine obtained from wild-type and Abcc6-knockout mice. The 2D data were compared to an improved 1D experiment in which signal contributions from macromolecules and the urea peak have been spectroscopically removed for more accurate quantitation of low-abundance metabolites. Although statistical models from both 1D and 2D data could differentiate samples acquired from the two groups of mice, only the 2D spectra allowed the characterization of statistically relevant changes in the low-abundance metabolites. While acquisition of the 2D data require more time, the data obtained resulted in a more meaningful and comprehensive metabolic profile, aided in metabolite identifications, and minimized ambiguities in peak assignments.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/pr700594s | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Observation of H-H J-couplings in fast magic-angle-spinning solid-state NMR spectroscopy.
Nat Commun
December 2024
Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland.
While H-H J-couplings are the cornerstone of all spectral assignment methods in solution-state NMR, they are yet to be observed in solids. Here we observe H-H J-couplings in plastic crystals of (1S)-(-)-camphor in solid-state NMR at magic angle spinning (MAS) rates of 100 kHz and above. This is enabled in this special case because the intrinsic coherence lifetimes at fast MAS rates become longer than the inverse of the H-H J couplings.
View Article and Find Full Text PDFIntegrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.
Nat Commun
December 2024
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany.
Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts.
View Article and Find Full Text PDFHigher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade.
Nat Commun
December 2024
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter.
View Article and Find Full Text PDFThe plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status.
Pediatr Rheumatol Online J
December 2024
Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.
Background: Juvenile idiopathic arthritis (JIA) is challenging to classify and effectively monitor due to the lack of disease- and subtype-specific biomarkers. A robust molecular signature that tracks with specific JIA features over time is urgently required, and targeted plasma metabolomics may reveal such a signature. The primary aim of this study was to characterise the differences in the plasma metabolome between JIA patients and non-JIA controls and identify specific markers of JIA subtype.
View Article and Find Full Text PDFInterpretable machine learning model for predicting clinically significant prostate cancer: integrating intratumoral and peritumoral radiomics with clinical and metabolic features.
BMC Med Imaging
December 2024
Department of MRI, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical University), 56 Jinsui Road, Xinxiang, Henan, 453000, China.
Background: To develop and validate an interpretable machine learning model based on intratumoral and peritumoral radiomics combined with clinicoradiological features and metabolic information from magnetic resonance spectroscopy (MRS), to predict clinically significant prostate cancer (csPCa, Gleason score ≥ 3 + 4) and avoid unnecessary biopsies.
Methods: This study retrospectively analyzed 350 patients with suspicious prostate lesions from our institution who underwent 3.0 Tesla multiparametric magnetic resonance imaging (mpMRI) prior to biopsy (training set, n = 191, testing set, n = 83, and a temporal validation set, n = 76).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!