1,721,010 research outputs found
Global skeletal muscle metabolomics reveals mechanisms behind higher response to resistance training in older adults
No full textResistance training (RT) is a highly effective intervention for combating frailty by improving muscle mass, strength, and function in aging. Older adults often show heterogeneous muscle-related responses to RT. The purpose of this study was to discover how responsiveness to RT manifests in muscle-specific metabolomic responses in a cohort of older adults.This study is a secondary analysis on the vastus lateralis muscle biopsies collected from a completed RT and whey protein supplementation trial. We utilised data from a total of 50 participants who performed unilateral knee extensions twice weekly for 10 weeks. One leg completed 1 set, and the other completed 4 sets of 8–15 repetitions. We analysed the 4-set condition, previously shown to induce greater muscle hypertrophy. Response variability was assessed using MRI-measured muscle cross-sectional area (CSA) changes. Responders were defined as those with hypertrophy exceeding the 1.7% method error. Quadriceps CSA in the lower responders (LowR) increased from 53.6 ± 12.1 cm² to 55.4 ± 12.8 cm² after 10 weeks of RT (3.3 ± 1.7%, P &lt; 0.001), and in higher responders (HighR) from 53.7 ± 12.5 cm² to 59.2 ± 13.6 cm² (10.3 ± 2.0%, P &lt; 0.001).Muscle biopsies were taken from the vastus lateralis before and after RT. We performed untargeted LC-MS metabolomics to investigate changes in muscle metabolic regulation. Partial least squares discriminant analysis (PLS-DA) using polar extracts achieved a 75% average correct classification rate for predicting HighR and LowR, validated using 1,000 bootstraps. We then performed N-way ANOVA on log-transformed metabolic features to test for differences before and after RT in HighR (n=25, mean age 67±4 years) vs. LowR (n=25, mean age 69±5 years).There were no significant differences in the baseline metabolomic profile. HighR participants showed greater relative levels of amino acids (e.g., isoleucine, leucine, valine, phenylalanine, lysine, glutamine, methionine, tyrosine, citrulline, tryptophan, kynurenine, indole) and gut-related metabolites (choline, indole, kynurenic acid, adrenaline, isoprenaline) (FDR &lt; 0.05). Several gut-derived metabolites were significantly elevated in HighR, including indole metabolites, 4-hydroxyhippurate, proline, and stachydrine (FDR &lt; 0.05). Pathway enrichment using Mummichog revealed significant enrichment of tyrosine, aspartate, and tryptophan metabolism (P-Fisher &lt; 0.05).Our findings identify branched-chain amino acid catabolism, tryptophan metabolism (indole and kynurenine pathways), the TCA cycle, gut-derived metabolites, carnosine, and acylcarnitine metabolism as prominent pathways disrupted in LowR. Metabolomics offers potential to improve intervention strategies to reduce sarcopenia and frailty in aging.</div
Metabolic response of Klebsiella oxytoca to ciprofloxacin exposure: a metabolomics approach
Full text linkIntroduction: Rapid detection and identification of pathogens and antimicrobial susceptibility is essential for guiding appropriate antimicrobial therapy and reducing morbidity and mortality associated with sepsis. Objectives: The metabolic response of clinical isolates of Klebsiella oxytoca exposed to different concentrations of ciprofloxacin (the second generation of quinolones antibiotics) were studied in order to investigate underlying mechanisms associated with antimicrobial resistance (AMR). Methods: Metabolomics investigations were performed using Fourier-transform infrared (FT-IR) spectroscopy as a metabolic fingerprinting approach combined with gas chromatography-mass spectrometry (GC-MS) for metabolic profiling. Results: Our findings demonstrated that metabolic fingerprints provided by FT-IR analysis allowed for the differentiation of susceptible and resistant isolates. GC-MS analysis validated these findings, while also providing a deeper understanding of the metabolic alterations caused by exposure to ciprofloxacin. GC-MS metabolic profiling detected 176 metabolic features in the cellular extracts cultivated on BHI broth, and of these, 137 could be identified to Metabolomics Standards Initiative Level 2. Data analysis showed that 40 metabolites (30 Level 2 and 10 unknown) were differentiated between susceptible and resistant isolates. The identified metabolites belonging to central carbon metabolism; arginine and proline metabolism; alanine, aspartate and glutamate metabolism; and pyruvate metabolism. Univariate receiver operating characteristic (ROC) curve analyses revealed that six of these metabolites (glycerol-3-phosphate, O-phosphoethanolamine, asparagine dehydrate, maleimide, tyrosine, and alanine) have a crucial role in distinguishing susceptible from resistant isolates (AUC > 0.84) and contributing to antimicrobial resistance in K. oxtytoca. Conclusion: Our study provides invaluable new insights into the mechanisms underlying development of antimicrobial resistance in K. oxytoca suggests potential therapeutic targets for prevention and identification of AMR in K. oxytoca infections
Application of Rapid Evaporative Ionization Mass Spectrometry (REIMS) to Identify Antimicrobial Resistance in Uropathogenic Escherichia coli (UPEC) Isolates via Deuterium Isotope Probing
Full text linkAntimicrobial resistance (AMR) continues to pose a significant threat to global health, undermining advances in modern medicine and increasing mortality from previously treatable infections. Rapid and accurate antimicrobial susceptibility testing (AST) is critical, both for effective judicious treatment and controlling the spread of AMR. For the first time, we demonstrate the application of rapid evaporative ionization mass spectrometry (REIMS), combined with deuterium isotope probing (DIP), as a novel approach for identifying AMR in uropathogenic Escherichia coli (UPEC) isolates within only a 1 h incubation period. By directly analyzing bacterial samples without extensive preparation, REIMS serves as a rapid fingerprinting tool, employing DIP and multivariate statistical analysis to provide AST profiling of UPEC isolates. Distinct clustering patterns were observed between trimethoprim-susceptible and trimethoprim-resistant UPEC isolates grown in media containing 10% deuterium oxide (D2O). TMP-susceptible isolates treated with trimethoprim displayed no significant deuterium incorporation, serving as an indicator of a lower metabolic activity resulting from antimicrobial action. We also demonstrated the ability to differentiate the origin of heavy water, confirming that deuterium incorporation was a biological process rather than of extracellular origin resulting from chemical processes. Several mass spectral bins showed patterns consistent with deuterated phospholipid species, including those in the expected mass range for phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), which are the most abundant phospholipids in E. coli. However, these annotations remain tentative, as no structural confirmation (e.g., MS/MS) was performed. These findings suggest that REIMS, combined with DIP and multivariate statistical analysis, serves as an efficient fast workflow for the rapid detection of AMR
The Role of Raman Spectroscopy Within Quantitative Metabolomics
Full text link Ninety-two years have passed since the discovery of the Raman effect, and there are currently more than 25 different types of Raman-based techniques. The past two decades have witnessed the blossoming of Raman spectroscopy as a powerful physicochemical technique with broad applications within the life sciences. In this review, we critique the use of Raman spectroscopy as a tool for quantitative metabolomics. We overview recent developments of Raman spectroscopy for identification and quantification of disease biomarkers in liquid biopsy, with a focus on the recent advances within surface-enhanced Raman scattering–based methods. Ultimately, we discuss the applications of imaging modalities based on Raman scattering as label-free methods to study the abundance and distribution of biomolecules in cells and tissues, including mammalian, algal, and bacterial cells. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 14 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. </jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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