Metabolomics and lipidomics: Expanding the molecular landscape of exercise biology

Dynamic changes in circulating and tissue metabolites and lipids occur in response to exercise-induced cellular and whole-body energy demands to maintain metabolic homeostasis. The metabolome and lipidome in a given biological system provides a molecular snapshot of these rapid and complex metabolic perturbations. The application of metabolomics and lipidomics to map the metabolic responses to an acute bout of aerobic/endurance or resistance exercise has dramatically expanded over the past decade thanks to major analytical advancements, with most exercise-related studies to date focused on analyzing human biofluids and tissues. Experimental and analytical con-siderations, as well as complementary studies using animal model systems, are warranted to help overcome challenges associated with large human interindividual variability and decipher the breadth of molecular mechanisms underlying the metabolic health-promoting effects of exercise. In this review, we provide a guide for exercise researchers regarding analytical techniques and experimental workflows commonly used in metabolomics and lipidomics. Furthermore, we discuss advancements in human and mammalian exercise research utilizing metabolomic and lipidomic approaches in the last decade, as well as highlight key technical considerations and remaining knowledge gaps to continue expanding the molecular landscape of exercise biology

Adoption Of ASL Classifiers As Delivered By Head-Mounted Displays In A Planetarium Show

Accommodating the planetarium experience to members of the deaf or hard-of-hearing community has often created situations that are either disruptive to the rest of the audience or provide an insufficient accommodation. To address this issue, we examined the use of head-mounted displays to deliver an American Sign Language sound track to learners in the planetarium Here we present results from a feasibility study to see if an ASL sound track delivered through a head-mount display can be understood by deaf junior to senior high aged students who are fluent in ASL. We examined the adoption of ASL classifiers that were used as part of the sound track for a full dome planetarium show. We found that about 90% of all students in our sample adopted at least one classifier from the show. In addition, those who viewed the sound track in a head-mounted display did at least as well as those who saw the sound track projected directly on the dome. These results suggest that ASL transmitted through head-mounted displays is a promising method to help improve learning for those whose primary language is ASL and merits further investigation

Metabolomics reveals mouse plasma metabolite responses to acute exercise and effects of disrupting AMPK-glycogen interactions

Introduction: The AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that becomes activated by exercise and binds glycogen, an important energy store required to meet exercise-induced energy demands. Disruption of AMPK-glycogen interactions in mice reduces exercise capacity and impairs whole-body metabolism. However, the mechanisms underlying these phenotypic effects at rest and following exercise are unknown. Furthermore, the plasma metabolite responses to an acute exercise challenge in mice remain largely uncharacterized. Methods : Plasma samples were collected from wild type (WT) and AMPK double knock-in (DKI) mice with disrupted AMPK-glycogen binding at rest and following 30-min submaximal treadmill running. An untargeted metabolomics approach was utilized to determine the breadth of plasma metabolite changes occurring in response to acute exercise and the effects of disrupting AMPK-glycogen binding. Results: Relative to WT mice, DKI mice had reduced maximal running speed (p \u3c 0.0001) concomitant with increased body mass (p \u3c 0.01) and adiposity (p \u3c 0.001). A total of 83 plasma metabolites were identified/annotated, with 17 metabolites significantly different (p \u3c 0.05; FDR \u3c 0.1) in exercised (↑ 6; ↓ 11) versus rested mice, including amino acids, acylcarnitines and steroid hormones. Pantothenic acid was reduced in DKI mice versus WT. Distinct plasma metabolite profiles were observed between the rest and exercise conditions and between WT and DKI mice at rest, while metabolite profiles of both genotypes converged following exercise. These differences in metabolite profiles were primarily explained by exercise-associated increases in acylcarnitines and steroid hormones as well as decreases in amino acids and derivatives following exercise. DKI plasma showed greater decreases in amino acids following exercise versus WT. Conclusion : This is the first study to map mouse plasma metabolomic changes following a bout of acute exercise in WT mice and the effects of disrupting AMPK-glycogen interactions in DKI mice. Untargeted metabolomics revealed alterations in metabolite profiles between rested and exercised mice in both genotypes, and between genotypes at rest. This study has uncovered known and previously unreported plasma metabolite responses to acute exercise in WT mice, as well as greater decreases in amino acids following exercise in DKI plasma. Reduced pantothenic acid levels may contribute to differences in fuel utilization in DKI mice

Lipidomic features of honey bee and colony health during limited supplementary feeding

Honey bee nutritional health depends on nectar and pollen, which provide the main source of carbohydrates, proteins and lipids to individual bees. During malnutrition, insect metabolism accesses fat body reserves. However, this process in bees and its repercussions at the colony level are poorly understood. Using untargeted lipidomics and gene expression analysis, we examined the effects of different feeding treatments (starvation, sugar feeding and sugar + pollen feeding) on bees and correlated them with colony health indicators. We found that nutritional stress led to an increase in unsaturated triacylglycerols and diacylglycerols, as well as a decrease in free fatty acids in the bee fat body. Here, we hypothesise that stored lipids are made available through a process where unsaturations change lipid\u27s structure. Increased gene expression of three lipid desaturases in response to malnutrition supports this hypothesis, as these desaturases may be involved in releasing fatty acyl chains for lipolysis. Although nutritional stress was evident in starving and sugar-fed bees at the colony and physiological level, only starved colonies presented long-term effects in honey production

Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection.

The metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma were characterized using multiplatform metabolic phenotyping with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Quantitative measurements of lipoprotein subfractions, α-1-acid glycoprotein, glucose, and biogenic amines were made on samples from symptomatic coronavirus disease 19 (COVID-19) patients who had tested positive for the SARS-CoV-2 virus (n = 17) and from age- and gender-matched controls (n = 25). Data were analyzed using an orthogonal-projections to latent structures (OPLS) method and used to construct an exceptionally strong (AUROC = 1) hybrid NMR-MS model that enabled detailed metabolic discrimination between the groups and their biochemical relationships. Key discriminant metabolites included markers of inflammation including elevated α-1-acid glycoprotein and an increased kynurenine/tryptophan ratio. There was also an abnormal lipoprotein, glucose, and amino acid signature consistent with diabetes and coronary artery disease (low total and HDL Apolipoprotein A1, low HDL triglycerides, high LDL and VLDL triglycerides), plus multiple highly significant amino acid markers of liver dysfunction (including the elevated glutamine/glutamate and Fischer's ratios) that present themselves as part of a distinct SARS-CoV-2 infection pattern. A multivariate training-test set model was validated using independent samples from additional SARS-CoV-2 positive patients and controls. The predictive model showed a sensitivity of 100% for SARS-CoV-2 positivity. The breadth of the disturbed pathways indicates a systemic signature of SARS-CoV-2 positivity that includes elements of liver dysfunction, dyslipidemia, diabetes, and coronary heart disease risk that are consistent with recent reports that COVID-19 is a systemic disease affecting multiple organs and systems. Metabolights study reference: MTBLS2014

Work-Unit Absenteeism: Effects of Satisfaction, Commitment, Labor Market Conditions, and Time

Prior research is limited in explaining absenteeism at the unit level and over time. We developed and tested a model of unit-level absenteeism using five waves of data collected over six years from 115 work units in a large state agency. Unit-level job satisfaction, organizational commitment, and local unemployment were modeled as time-varying predictors of absenteeism. Shared satisfaction and commitment interacted in predicting absenteeism but were not related to the rate of change in absenteeism over time. Unit-level satisfaction and commitment were more strongly related to absenteeism when units were located in areas with plentiful job alternatives

PPARα Deficiency in Inflammatory Cells Suppresses Tumor Growth

Inflammation in the tumor bed can either promote or inhibit tumor growth. Peroxisome proliferator-activated receptor (PPAR)α is a central transcriptional suppressor of inflammation, and may therefore modulate tumor growth. Here we show that PPARα deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of the endogenous angiogenesis inhibitor thrombospondin-1 and prevents tumor growth. Bone marrow transplantation and granulocyte depletion show that PPARα expressing granulocytes are necessary for tumor growth. Neutralization of thrombospondin-1 restores tumor growth in PPARα-deficient mice. These findings suggest that the absence of PPARα activity renders inflammatory infiltrates tumor suppressive and, thus, may provide a target for inhibiting tumor growth by modulating stromal processes, such as angiogenesis

Complete Genome Sequence of the Complex Carbohydrate-Degrading Marine Bacterium, Saccharophagus degradans Strain 2-40T

The marine bacterium Saccharophagus degradans strain 2-40 (Sde 2-40) is emerging as a vanguard of a recently discovered group of marine and estuarine bacteria that recycles complex polysaccharides. We report its complete genome sequence, analysis of which identifies an unusually large number of enzymes that degrade >10 complex polysaccharides. Not only is this an extraordinary range of catabolic capability, many of the enzymes exhibit unusual architecture including novel combinations of catalytic and substrate-binding modules. We hypothesize that many of these features are adaptations that facilitate depolymerization of complex polysaccharides in the marine environment. This is the first sequenced genome of a marine bacterium that can degrade plant cell walls, an important component of the carbon cycle that is not well-characterized in the marine environment

SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2, which is now completed, measured medium-resolution (R=1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa