Featured
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| Open AccessDIAMetAlyzer allows automated false-discovery rate-controlled analysis for data-independent acquisition in metabolomics
The extraction of meaningful biological knowledge from high-throughput mass spectrometry data relies on limiting false discoveries to a manageable amount. Here the authors establish an automated, false discovery rate-controlled targeted analysis workflow for data-independent acquisition that enables a robust FDR estimation improving the comparability of results in the metabolomics field.
- Oliver Alka
- , Premy Shanthamoorthy
- & Hannes L. Röst
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Article
| Open AccessIn vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization
Bradyzoites are a quiescent form of Toxoplasma gondii enclosed in cysts during chronic infections. Here, Christiansen et al. develop a human myotube-based in vitro culture model of cysts that are infectious to mice and characterize their metabolism in comparison to fast replicating tachyzoites.
- Céline Christiansen
- , Deborah Maus
- & Martin Blume
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Article
| Open AccessComparative metabolomics with Metaboseek reveals functions of a conserved fat metabolism pathway in C. elegans
Untargeted mass spectrometry-based metabolomics can reveal new biochemistry, but data analysis is challenging. Here, the authors develop Metaboseek, an open-source software that facilitates metabolite discovery, and apply it to characterize fatty acid alpha-oxidation in C. elegans.
- Maximilian J. Helf
- , Bennett W. Fox
- & Frank C. Schroeder
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Article
| Open AccessPantothenate biosynthesis is critical for chronic infection by the neurotropic parasite Toxoplasma gondii
Coenzyme A (CoA) is an essential metabolite found in all organisms and its synthesis involves five conserved enzymatic steps and uses pantothenate (Pan) as a precursor. Here, Lunghi et al. examine the Pan synthesis pathway in Toxoplasma gondii and find that Pan is crucial for the establishment of chronic but not acute infection.
- Matteo Lunghi
- , Joachim Kloehn
- & Dominique Soldati-Favre
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Article
| Open AccessPhosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
Glycerol-3-phosphate phosphatase is a recently discovered enzyme at the heart of metabolism. Here, the authors used C. elegans and showed that its activation promotes stress resistance, healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility.
- Elite Possik
- , Clémence Schmitt
- & Marc Prentki
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Article
| Open AccessOxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation
Oxylipins are lipid mediators generated during infection for regulating inflammatory responses, but how they are removed is not completely clear. Here the authors show that cellular oxylipin removal is linked to mitochondria β-oxidation by CPT1, a mitochondria lipid importer protein, to serve as a metabolic checkpoint for oxylipin homeostasis and inflammation.
- Mariya Misheva
- , Konstantinos Kotzamanis
- & Valerie B. O’Donnell
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Article
| Open AccessClenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells
In this study, the authors demonstrated that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling may prove beneficial as novel antidiabetic drugs.
- Jaroslawna Meister
- , Derek B. J. Bone
- & Jürgen Wess
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Article
| Open AccessBST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities
Nicotinamide riboside (NR) is a NAD + precursor exhibiting beneficial effects against aging. Here the authors demonstrate that orally administered NR increases NAD + levels in a diphasic manner and that bone marrow stromal cell antigen 1 plays a crucial role for NAD + synthesis from NR.
- Keisuke Yaku
- , Sailesh Palikhe
- & Takashi Nakagawa
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Article
| Open AccessEvolutionary metabolic landscape from preneoplasia to invasive lung adenocarcinoma
Metabolic reprogramming occurs during tumor progression. Here the authors decipher metabolic trajectories from preneoplasia to lung adenocarcinoma in tumor samples and identify plasma metabolites as potential predictive biomarkers for early detection.
- Meng Nie
- , Ke Yao
- & Zeping Hu
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Article
| Open AccessConstitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243 A > G mtDNA mutation
Heteroplasmic mtDNA mutations cause disease in humans. Here, Chung et al find the PI3K-Akt-mTORC1 pathway constitutively activated in cells with the heteroplasmic m.3243 A > G mutation, and inhibition of the pathway cell autonomously reduces mutant mtDNA load and rescues mitochondrial bioenergetics.
- Chih-Yao Chung
- , Kritarth Singh
- & Michael R. Duchen
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Article
| Open AccessRIPK1 regulates starvation resistance by modulating aspartate catabolism
RIPK1 is critical for normal development and cell death. Here, the authors identify a metabolic role for RIPK1 in aspartate homeostasis, as increased aspartate levels in RIPK1-deficient cells inhibits starvation-induced autophagy by ULK1.
- Xinyu Mei
- , Yuan Guo
- & Zheng-Jiang Zhu
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Article
| Open AccessHigh-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice
The gut microbiota harbours neuroactive potential with links to neurological disorders. Here, the authors apply global metabolomics with an integrated annotation strategy to comparatively profile fecal, blood serum and cerebral cortical brain tissues of eight-week-old germ-free mice vs. age-matched specific-pathogen-free mice, providing a snapshot of the metabolome status linked to the gut-brain axis.
- Yunjia Lai
- , Chih-Wei Liu
- & Kun Lu
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Article
| Open AccessA metabolome atlas of the aging mouse brain
Metabolites play an important role in physiology, yet the complexity of the metabolome and its interaction with disease and aging is poorly understood. Here the authors present a comprehensive atlas of the mouse brain metabolome and how it changes during aging.
- Jun Ding
- , Jian Ji
- & Oliver Fiehn
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Article
| Open AccessFinger sweat analysis enables short interval metabolic biomonitoring in humans
Biomonitoring of sweat from fingertips overcomes current limitations in time-resolved metabolomic profiling of humans and may prove to become a powerful, noninvasive tool for precision medicine. Here, in a feasibility study of short interval sampling of sweat from fingertips, the authors assay individual dynamic metabolic patterns of endogenous and exogenous molecules.
- Julia Brunmair
- , Mathias Gotsmy
- & Christopher Gerner
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Comment
| Open AccessThe growing need for controlled data access models in clinical proteomics and metabolomics
More and more clinical studies include potentially sensitive human proteomics or metabolomics datasets, but bioinformatics resources for managing the access to these data are not yet available. This commentary discusses current best practices and future perspectives for the responsible handling of clinical proteomics and metabolomics data.
- Thomas M. Keane
- , Claire O’Donovan
- & Juan Antonio Vizcaíno
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Article
| Open AccessExtensive regulation of enzyme activity by phosphorylation in Escherichia coli
While phosphorylation is an essential post-translational modification in eukaryotes only recently the phosphoproteome of prokaryotes has been provided. Here, Schastnaya et al. mutate 52 phosphosites on 23 E. coli enzymes and apply metabolomics to provide evidence for the functional relevance of bacterial phosphorylation events.
- Evgeniya Schastnaya
- , Zrinka Raguz Nakic
- & Uwe Sauer
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Article
| Open AccessA scalable workflow to characterize the human exposome
Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.
- Xin Hu
- , Douglas I. Walker
- & Dean P. Jones
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Article
| Open AccessPeak learning of mass spectrometry imaging data using artificial neural networks
The high dimensional and complex nature of mass spectrometry imaging (MSI) data poses challenges to downstream analyses. Here the authors show an application of artificial intelligence in mining MSI data revealing biologically relevant metabolomic and proteomic information from data acquired on different mass spectrometry platforms.
- Walid M. Abdelmoula
- , Begona Gimenez-Cassina Lopez
- & Nathalie Y. R. Agar
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Article
| Open AccessLarge scale enzyme based xenobiotic identification for exposomics
Humans are exposed to many xenobiotic chemicals, but identification of low abundance xenobiotic exposures is limited by a lack of authentic standards for xenobiotic metabolites. Here the authors develop methods for enzymatic generation of diverse xenobiotic metabolites for use with high-resolution mass spectrometry for biology-based chemical identification.
- Ken H. Liu
- , Choon M. Lee
- & Dean P. Jones
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Article
| Open AccessMiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer
Cholesterol metabolism is involved in the progression of aggressive prostate cancer (PCa). Here the authors show that miR-205 downregulation promotes cholesterol synthesis and androgen receptor signalling in PCa through enhancing the expression of the rate-limiting enzyme of cholesterol synthesis, squalene epoxidase.
- C. Kalogirou
- , J. Linxweiler
- & A. Schulze
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Article
| Open AccessA hierarchical approach to removal of unwanted variation for large-scale metabolomics data
Mass spectrometry-based metabolomics is a powerful method for profiling large clinical cohorts but batch variations can obscure biologically meaningful differences. Here, the authors develop a computational workflow that removes unwanted data variation while preserving biologically relevant information.
- Taiyun Kim
- , Owen Tang
- & Jean Yee Hwa Yang
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Article
| Open AccessSpontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters
Analogues of α-ketoglutarate are used in many cellular studies but assumptions are made about cellular uptake. Here, the authors show that esterified analogues rapidly hydrolyse in aqueous medium resulting in an analogue which can be quickly taken up by many cell lines, contrary to prevailing assumptions.
- Seth J. Parker
- , Joel Encarnación-Rosado
- & Alec C. Kimmelman
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Article
| Open AccessTwo parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis
The metabolism of amino acids and the cellular energy sensor AMPK are both connected to mTORC1, but the pathway details have not been well defined. Here, the authors show that glutamine metabolism and mTORC1 have two regulatory connections with relevance to cancer therapeutics design.
- Clément Bodineau
- , Mercedes Tomé
- & Raúl V. Durán
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Article
| Open AccessGlucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development
Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.
- Jianli He
- , Xun Shangguan
- & Jinke Cheng
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Article
| Open AccessIon mobility-based sterolomics reveals spatially and temporally distinctive sterol lipids in the mouse brain
Sterol lipids are crucial for maintaining proper brain function. Here, the authors combine ion mobility-mass spectrometry and machine learning to assemble a sterol lipid library and characterize differences in sterol lipids across ten brain regions and two age groups in mice.
- Tongzhou Li
- , Yandong Yin
- & Zheng-Jiang Zhu
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Article
| Open AccessHexosamine biosynthetic pathway and O-GlcNAc-processing enzymes regulate daily rhythms in protein O-GlcNAcylation
Misalignment between lifestyle and the natural day-night cycle, such as mistimed eating, can negatively impact health. Here the authors show that mistimed feeding alters protein O-GlcNAcylation, a nutrient sensitive post-translational modification.
- Xianhui Liu
- , Ivana Blaženović
- & Joanna C. Chiu
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Article
| Open AccessIon identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment
Molecular networking connects molecules based on their fragment ion mass spectra (MS2), but may leave adduct species from the same molecular family separate. To address this issue, the authors develop a networking approach that fuses MS1- and MS2-based networks and integrate it into the GNPS environment.
- Robin Schmid
- , Daniel Petras
- & Pieter C. Dorrestein
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Article
| Open AccessMolDiscovery: learning mass spectrometry fragmentation of small molecules
A large number of mass spectra from different samples have been collected, and to identify small molecules from these spectra, database searches are needed, which is challenging. Here, the authors report molDiscovery, a mass spectral database search method that uses an algorithm to generate mass spectrometry fragmentations and learns a probabilistic model to match small molecules with their mass spectra.
- Liu Cao
- , Mustafa Guler
- & Hosein Mohimani
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Article
| Open AccessRegulation of the one carbon folate cycle as a shared metabolic signature of longevity
Metabolic pathways are closely intertwined with longevity. Here the authors perform metabolomic profiling of canonical longevity pathways and show that folate and methionine cycle intermediates are changed in common, and further, genetic manipulation of pathway enzymes and supplementation with metabolites indicates that they causally regulate longevity.
- Andrea Annibal
- , Rebecca George Tharyan
- & Adam Antebi
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Article
| Open AccessLow chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk
Abnormal placentation is associated with recurrent spontaneous abortion (RSA) risk. Here the authors report that low embryonic villous succinate level associates with risk of RSA in patients, and increasing succinate levels is sufficient to reduce the incidence rate in a mouse model of spontaneous abortion.
- Xiao-Hui Wang
- , Sha Xu
- & Jian-Yuan Zhao
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Article
| Open AccessPareto optimality between growth-rate and lag-time couples metabolic noise to phenotypic heterogeneity in Escherichia coli
It is unclear how noise in gene expression propagates to phenotypic heterogeneity in clonal bacterial populations. Here, the authors explore how variability in central sugar metabolism in E. coli can mediate and promote population diversification.
- Diego Antonio Fernandez Fuentes
- , Pablo Manfredi
- & Mattia Zampieri
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Article
| Open AccessBrown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis
Beige and brown fat may influence systemic metabolism through secreted signals. Here the authors identify a panel of metabolites secreted from beige and brown fat cells, which signal to influence fat tissue and skeletal muscle metabolism and have anti-obesity effects in mouse models of obesity and diabetes.
- Anna Whitehead
- , Fynn N. Krause
- & Lee D. Roberts
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Comment
| Open AccessCross-kingdom metabolic manipulation promotes Salmonella replication inside macrophages
Replication inside macrophages is crucial for systemic dissemination of Salmonella in hosts. In a Nature Communications article, Jiang et al. show that Salmonella stimulates glycolysis and represses serine synthesis in macrophages, leading to accumulation of host glycolytic intermediates that the bacteria use as carbon source and as cues for its replication.
- Deyanira Pérez-Morales
- & Víctor H. Bustamante
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Article
| Open AccessDissection of two routes to naïve pluripotency using different kinase inhibitors
Naïve pluripotency can be stabilized through different pharmacological approaches. Here, the authors profile temporal changes of protein phosphorylation, proteome and metabolome as mESCs transition to the naïve state in response to two pharmacological treatments, revealing general and treatment-specific processes.
- Ana Martinez-Val
- , Cian J. Lynch
- & Javier Munoz
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Article
| Open AccessBranched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart
Systemic modulation of branched-chain keto acid (BCKA) metabolism alters cardiac health. Here, the authors define the major fates of BCKA in the heart and demonstrate that acute exposure to BCKA levels found in obesity activates cardiac protein synthesis and markedly alters the heart phosphoproteome.
- Jacquelyn M. Walejko
- , Bridgette A. Christopher
- & Robert W. McGarrah
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Article
| Open AccessSARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication
Viruses rely on host metabolism for replication. Here, the authors perform transcriptional and metabolomic analyses at 8 hours after SARS-CoV-2 infection and find that the virus alters host folate and one-carbon metabolism at a post-transcriptional level.
- Yuchen Zhang
- , Rui Guo
- & Benjamin E. Gewurz
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Article
| Open AccessIntegrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications
Metabolism changes can modulate immune responses in many contexts, and vice versa. Here the authors associate metabolomic, as well as cytokine and chemokine, data from stratified COVID-19 patients to find that arginine, tryptophan and purine metabolic pathways correlate with hyperproliferation, thus hinting at potential therapeutic targets for severe COVID-19 patients.
- Nan Xiao
- , Meng Nie
- & Zeping Hu
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Article
| Open AccessEndogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma
Volatile aldehydes can be enriched in esophageal adenocarcinoma patients’ breath. Here, the authors reveal corresponding metabolic changes in EAC tumours, which may be caused by impaired detoxification of endogenous metabolites.
- Stefan Antonowicz
- , Zsolt Bodai
- & George B. Hanna
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Article
| Open AccessStaphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation
The authors show that the pathogen Staphylococcus aureus induces a distinct airway immunometabolic response, dominated by release of itaconate. This metabolite, in turn, potentiates extracellular polysaccharide synthesis and biofilm formation in S. aureus, which may facilitate chronic infection.
- Kira L. Tomlinson
- , Tania Wong Fok Lung
- & Sebastián A. Riquelme
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Article
| Open AccessFructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation
Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype owing to excess pro-inflammatory cytokine production.
- Nicholas Jones
- , Julianna Blagih
- & Catherine A. Thornton
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Article
| Open AccessSalmonella Typhimurium reprograms macrophage metabolism via T3SS effector SopE2 to promote intracellular replication and virulence
Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here, Jiang et al. show that infected macrophages exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates that promote intracellular replication and virulence of S. Typhimurium.
- Lingyan Jiang
- , Peisheng Wang
- & Lei Wang
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Article
| Open AccessMOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.
- Joseph C. Reynolds
- , Rochelle W. Lai
- & Changhan Lee
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Article
| Open AccessRhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells
Red blood cells, which do not possess a nucleus, have circadian redox rhythms with incompletely understood regulatory mechanisms. Here the authors show that glucose metabolism plays a crucial role in regulating circadian redox status of human red blood cells.
- Ratnasekhar Ch
- , Guillaume Rey
- & Akhilesh B. Reddy
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Article
| Open AccessChromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis
Ophiorrhiza pumila is a medicinal plant that can produce the anti-cancer monoterpene indole alkaloid (MIA) camptothecin. Here, the authors report its genome assembly and propose a working model for MIA evolution and biosynthesis through comparative genomics, synteny, and metabolic gene cluster analyses.
- Amit Rai
- , Hideki Hirakawa
- & Mami Yamazaki
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Article
| Open AccessUsing metacommunity ecology to understand environmental metabolomes
Despite growing interest in environmental metabolomics, we lack conceptual frameworks for considering how metabolites vary across space and time in ecological systems. Here, the authors apply (species) community assembly concepts to metabolomics data, offering a way forward in understanding the assembly of metabolite assemblages.
- Robert E. Danczak
- , Rosalie K. Chu
- & James C. Stegen
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Article
| Open AccessD-mannose suppresses macrophage IL-1β production
Mannose is present at trace levels in blood and regulates cancer growth. Here the authors show that supraphysiological levels of mannose can also regulate macrophages, limiting their production of IL-1β and increasing resistance of mice to LPS-induced endotoxemia and DSS-induced colitis.
- Simone Torretta
- , Alessandra Scagliola
- & Simone Cardaci
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Article
| Open AccessAnalysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry
Myo-Inositol phosphates (InsPs) and pyrophosphates (PP-InsPs) are important second messengers but their analysis remains challenging. Here, the authors develop a capillary electrophoresis-mass spectrometry method for the identification and quantitation of InsP and PP-InsP isomers in cells and tissues.
- Danye Qiu
- , Miranda S. Wilson
- & Henning J. Jessen
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Article
| Open AccessConcordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease
The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
- Kevin Huynh
- , Wei Ling Florence Lim
- & Peter J. Meikle
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Article
| Open AccessSub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples
The analysis of metabolites offers promises in biomarker discovery. Here the authors demonstrate the metabolomics analysis of sub-nanoliter samples using triboelectric nanogenerator inductive nanoelectrospray ionization, which they apply to exhaled breath condensate from cystic fibrosis patients and mesenchymal stromal cells.
- Yafeng Li
- , Marcos Bouza
- & Facundo M. Fernández