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Translational Exercise Biomedicine May 2024'OMICs encapsulates study of scaled data acquisition, at the levels of DNA, RNA, protein, and metabolite species. The broad objectives of OMICs in biomedical exercise... (Review)
Review
OBJECTIVES
'OMICs encapsulates study of scaled data acquisition, at the levels of DNA, RNA, protein, and metabolite species. The broad objectives of OMICs in biomedical exercise research are multifarious, but commonly relate to biomarker development and understanding features of exercise adaptation in health, ageing and metabolic diseases.
METHODS
This field is one of exponential technical (i.e., depth of feature coverage) and scientific (i.e., in health, metabolic conditions and ageing, multi-OMICs) progress adopting and approaches.
RESULTS
Key findings in exercise biomedicine have led to the identification of OMIC features linking to heritability or adaptive responses to exercise e.g., the forging of GWAS/proteome/metabolome links to cardiovascular fitness and metabolic health adaptations. The recent addition of stable isotope tracing to proteomics ('dynamic proteomics') and metabolomics ('fluxomics') represents the next phase of state-of-the-art in 'OMICS.
CONCLUSIONS
These methods overcome limitations associated with point-in-time 'OMICs and can be achieved using substrate-specific tracers or deuterium oxide (DO), depending on the question; these methods could help identify how individual protein turnover and metabolite flux may explain exercise responses. We contend application of these methods will shed new light in translational exercise biomedicine.
PubMed: 38660119
DOI: 10.1515/teb-2024-2006 -
Journal of Animal Science Jan 2024The aim of the study was to investigate whether increased inclusion of sugar beet pulp (SBP) alters retention of fat, protein, and energy when backfat (BF) is restored...
The aim of the study was to investigate whether increased inclusion of sugar beet pulp (SBP) alters retention of fat, protein, and energy when backfat (BF) is restored in early- and mid-gestation. In total, 46 sows were fed one of four dietary treatments with increasing inclusion of SBP providing dietary fiber (DF) levels of 119, 152, 185, and 217 g/kg; sows were assigned to one of three feeding strategies (FS; high, medium, and low) depending on BF thickness at mating and again at day 30 for the following month. On days 0, 30, 60, and 108, body weight (BW) and BF thickness were measured and body pools of protein and fat were estimated using the deuterium oxide technique. On days 30 and 60, urine, feces, and blood samples were collected to quantify metabolites, energy, and nitrogen (N) balances. On days 15 and 45, heart rate was recorded to estimate heat energy. At farrowing, total born and weight of the litter were recorded. In early gestation, BW gain (P < 0.01) and body protein retention increased (P < 0.05) with increasing fiber inclusion, while body fat retention increased numerically by 59%. The increase in BF was greatest for sows fed the high FS, intermediate when fed the medium strategy, and negligible for sows fed the lowest FS (P < 0.001). Nitrogen intake, N loss in feces, and N balance increased linearly, whereas N loss in urine tended to decrease with increasing inclusion of fibers in early gestation. Concomitantly, fecal energy output and energy lost as methane increased linearly (P < 0.001), while energy output in urine declined linearly. Total metabolizable energy (ME) intake therefore increased from 36.5 MJ ME/d in the low fiber group to 38.5 MJ ME/d in the high fiber group (P < 0.01). Changing the ME towards more ketogenic energy was expected to favor fat retention rather than protein retention. However, due to increased intake of ME and increased N efficiency with increasing fiber inclusion, the sows gained more weight and protein with increasing fiber inclusion. In conclusion, increased feed intake improved both fat and protein retention, whereas increased DF intake increased protein retention.
Topics: Animals; Dietary Fiber; Female; Animal Feed; Pregnancy; Energy Metabolism; Animal Nutritional Physiological Phenomena; Diet; Swine; Beta vulgaris; Adipose Tissue
PubMed: 38659196
DOI: 10.1093/jas/skae092 -
Physics in Medicine and Biology May 2024. Prompt gamma timing (PGT) uses the detection time of prompt gammas emitted along the range of protons in proton radiotherapy to verify the position of the Bragg peak...
. Prompt gamma timing (PGT) uses the detection time of prompt gammas emitted along the range of protons in proton radiotherapy to verify the position of the Bragg peak (BP). Cherenkov detectors offer the possibility of enhanced signal-to-noise ratio (SNR) due to the inherent physics of Cherenkov emission which enhances detection of high energy prompt gamma rays relative to other induced uncorrelated signals. In this work, the PGT technique was applied to 3 semiconductor material slabs that emit only Cherenkov light for use in a full scale system: a 3 × 3 × 20 mmTlBr, a 12 × 12 × 12 mmTlBr, and a 5 × 5 × 5 mmTlCl.. A polymethyl methacrylate (PMMA) target was exposed to a 67.5 MeV, 0.5 nA proton beam and shifted in 3 mm increments at the Crocker nuclear laboratory (CNL) in Davis, CA, USA. A fast plastic scintillator coupled to a photomultiplier tube (PMT) provided the start reference for the proton time of flight. Time of flight (TOF) distributions were generated using this reference and the gamma-ray timestamp in the Cherenkov detector.. The SNR of the proton correlated peaks relative to the background was 20, 29, and 30 for each of the three samples, respectively. The upper limit of the position resolutions with the TlCl sample were 2 mm, 3 mm, and 5 mm for 30k, 10k, and 5k detected events, respectively. The time distribution of events with respect to the reference reproduced with clarity the periodicity of the beam, implying a very high SNR of the Cherenkov crystals to detect prompt gammas. Background presence from the neutron-induced continuum, prompt gammas from deuterium, or positron activation were not observed. Material choice and crystal dimensions did not seem to affect significantly the outcome of the results.. These results show the high SNR of the pure Cherenkov emitters TlBr and TlCl for the detection of prompt gammas in a proton beam with current of clinical significance and their potential for verifying the proton range. The accuracy in determining shifts of the BP was highly dependent on the number of events acquired, therefore, the performance of these detectors are expected to vary with different beam conditions such as current, pulse repetition, and proton bunch width.
Topics: Gamma Rays; Time Factors; Proton Therapy; Thallium; Lutetium; Protons; Polymethyl Methacrylate
PubMed: 38657638
DOI: 10.1088/1361-6560/ad4304 -
Frontiers in Plant Science 2024, the causal agent of Fusarium head blight (FHB), produces various mycotoxins that contaminate wheat grains and cause profound health problems in humans and animals....
, the causal agent of Fusarium head blight (FHB), produces various mycotoxins that contaminate wheat grains and cause profound health problems in humans and animals. Deoxynivalenol (DON) is the most common trichothecene found in contaminated grains. Our previous study showed that Arabidopsis-expressing trichothecene 3--acetyltransferase () converted DON to 3-acetyldeoxynivalenol (3-ADON) and excreted it outside of Arabidopsis cells. To determine if wheat can convert and excrete 3-ADON and reduce FHB and DON contamination, was cloned and introduced into wheat cv Bobwhite. Four independent transgenic lines containing were identified. Gene expression studies showed that was highly expressed in wheat leaf and spike tissues in the transgenic line FgTri101-1606. The seedlings of two FgTri101 transgenic wheat lines (FgTri101-1606 and 1651) grew significantly longer roots than the controls on media containing 5 µg/mL DON; however, the 3-ADON conversion and excretion was detected inconsistently in the seedlings of FgTri101-1606. Further analyses did not detect 3-ADON or other possible DON-related products in FgTri101-1606 seedlings after adding deuterium-labeled DON into the growth media. FgTri101-transgenic wheat plants showed significantly enhanced FHB resistance and lower DON content after they were infected with , but 3-ADON was not detected. Our study suggests that it is promising to utilize , a gene that the fungus uses for self-protection, for managing FHB and mycotoxin in wheat production.
PubMed: 38650698
DOI: 10.3389/fpls.2024.1389605 -
Human Brain Mapping Apr 2024Deuterium metabolic imaging (DMI) is an emerging magnetic resonance technique, for non-invasive mapping of human brain glucose metabolism following oral or intravenous...
Deuterium metabolic imaging (DMI) is an emerging magnetic resonance technique, for non-invasive mapping of human brain glucose metabolism following oral or intravenous administration of deuterium-labeled glucose. Regional differences in glucose metabolism can be observed in various brain pathologies, such as Alzheimer's disease, cancer, epilepsy or schizophrenia, but the achievable spatial resolution of conventional phase-encoded DMI methods is limited due to prolonged acquisition times rendering submilliliter isotropic spatial resolution for dynamic whole brain DMI not feasible. The purpose of this study was to implement non-Cartesian spatial-spectral sampling schemes for whole-brain H FID-MR Spectroscopic Imaging to assess time-resolved metabolic maps with sufficient spatial resolution to reliably detect metabolic differences between healthy gray and white matter regions. Results were compared with lower-resolution DMI maps, conventionally acquired within the same session. Six healthy volunteers (4 m/2 f) were scanned for ~90 min after administration of 0.8 g/kg oral [6,6']-H glucose. Time-resolved whole brain H FID-DMI maps of glucose (Glc) and glutamate + glutamine (Glx) were acquired with 0.75 and 2 mL isotropic spatial resolution using density-weighted concentric ring trajectory (CRT) and conventional phase encoding (PE) readout, respectively, at 7 T. To minimize the effect of decreased signal-to-noise ratios associated with smaller voxels, low-rank denoising of the spatiotemporal data was performed during reconstruction. Sixty-three minutes after oral tracer uptake three-dimensional (3D) CRT-DMI maps featured 19% higher (p = .006) deuterium-labeled Glc concentrations in GM (1.98 ± 0.43 mM) compared with WM (1.66 ± 0.36 mM) dominated regions, across all volunteers. Similarly, 48% higher (p = .01) H-Glx concentrations were observed in GM (2.21 ± 0.44 mM) compared with WM (1.49 ± 0.20 mM). Low-resolution PE-DMI maps acquired 70 min after tracer uptake featured smaller regional differences between GM- and WM-dominated areas for H-Glc concentrations with 2.00 ± 0.35 mM and 1.71 ± 0.31 mM, respectively (+16%; p = .045), while no regional differences were observed for H-Glx concentrations. In this study, we successfully implemented 3D FID-MRSI with fast CRT encoding for dynamic whole-brain DMI at 7 T with 2.5-fold increased spatial resolution compared with conventional whole-brain phase encoded (PE) DMI to visualize regional metabolic differences. The faster metabolic activity represented by 48% higher Glx concentrations was observed in GM- compared with WM-dominated regions, which could not be reproduced using whole-brain DMI with the low spatial resolution protocol. Improved assessment of regional pathologic alterations using a fully non-invasive imaging method is of high clinical relevance and could push DMI one step toward clinical applications.
Topics: Humans; Glucose; Deuterium; Adult; Male; Female; Brain; Magnetic Resonance Imaging; Young Adult; Magnetic Resonance Spectroscopy; Gray Matter; White Matter
PubMed: 38647048
DOI: 10.1002/hbm.26686 -
Cancer Research Jun 2024Metabolic subtypes of glioblastoma (GBM) have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential...
UNLABELLED
Metabolic subtypes of glioblastoma (GBM) have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. In this study, we used 2H magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging (MRSI) measurements of [6,6'-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived GBM xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial tricarboxylic acid cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6'-2H2]glucose, which are markers of glycolytic activity. Two cell lines representative of a glycolytic subtype and two representative of a mitochondrial subtype were identified. 2H magnetic resonance spectroscopy and MRSI measurements showed similar concentrations of 2H-labeled glucose from [6,6'-2H2]glucose in all four tumor models when implanted orthotopically in mice. The glycolytic subtypes showed higher concentrations of 2H-labeled lactate than the mitochondrial subtypes and normal-appearing brain tissue, whereas the mitochondrial subtypes showed more glutamate/glutamine labeling, a surrogate for tricarboxylic acid cycle activity, than the glycolytic subtypes and normal-appearing brain tissue. The response of the tumors to chemoradiation could be detected within 24 hours of treatment completion, with the mitochondrial subtypes showing a decrease in both 2H-labeled glutamate/glutamine and lactate concentrations and glycolytic tumors showing a decrease in 2H-labeled lactate concentration. This technique has the potential to be used clinically for treatment selection and early detection of treatment response.
SIGNIFICANCE
Deuterium magnetic resonance spectroscopic imaging of glucose metabolism has the potential to differentiate between glycolytic and mitochondrial metabolic subtypes in glioblastoma and to evaluate early treatment responses, which could guide patient treatment.
Topics: Glioblastoma; Humans; Animals; Mice; Brain Neoplasms; Deuterium; Glucose; Chemoradiotherapy; Cell Line, Tumor; Glycolysis; Xenograft Model Antitumor Assays; Mitochondria; Magnetic Resonance Spectroscopy; Magnetic Resonance Imaging; Female
PubMed: 38635885
DOI: 10.1158/0008-5472.CAN-23-2552 -
Communications Biology Apr 2024Cytosolic Ca and Na allosterically regulate Na/Ca exchanger (NCX) proteins to vary the NCX-mediated Ca entry/exit rates in diverse cell types. To resolve the...
Cytosolic Ca and Na allosterically regulate Na/Ca exchanger (NCX) proteins to vary the NCX-mediated Ca entry/exit rates in diverse cell types. To resolve the structure-based dynamic mechanisms underlying the ion-dependent allosteric regulation in mammalian NCXs, we analyze the apo, Ca, and Na-bound species of the brain NCX1.4 variant using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulations. Ca binding to the cytosolic regulatory domains (CBD1 and CBD2) rigidifies the intracellular regulatory loop (5L6) and promotes its interaction with the membrane domains. Either Na or Ca stabilizes the intracellular portions of transmembrane helices TM3, TM4, TM9, TM10, and their connecting loops (3L4 and 9L10), thereby exposing previously unappreciated regulatory sites. Ca or Na also rigidifies the palmitoylation domain (TMH2), and neighboring TM1/TM6 bundle, thereby uncovering a structural entity for modulating the ion transport rates. The present analysis provides new structure-dynamic clues underlying the regulatory diversity among tissue-specific NCX variants.
Topics: Animals; Protein Structure, Secondary; Mammals; Sodium-Calcium Exchanger
PubMed: 38627576
DOI: 10.1038/s42003-024-06159-9 -
Tree Physiology May 2024The oxygen and hydrogen isotopic composition (δ18O, δ2H) of plant tissues are key tools for the reconstruction of hydrological and plant physiological processes and...
The oxygen and hydrogen isotopic composition (δ18O, δ2H) of plant tissues are key tools for the reconstruction of hydrological and plant physiological processes and may therefore be used to disentangle the reasons for tree mortality. However, how both elements respond to soil drought conditions before death has rarely been investigated. To test this, we performed a greenhouse study and determined predisposing fertilization and lethal soil drought effects on δ18O and δ2H values of organic matter in leaves and tree rings of living and dead saplings of five European tree species. For mechanistic insights, we additionally measured isotopic (i.e. δ18O and δ2H values of leaf and twig water), physiological (i.e. leaf water potential and gas-exchange) and metabolic traits (i.e. leaf and stem non-structural carbohydrate concentration, carbon-to-nitrogen ratios). Across all species, lethal soil drought generally caused a homogenous 2H-enrichment in leaf and tree-ring organic matter, but a low and heterogenous δ18O response in the same tissues. Unlike δ18O values, δ2H values of tree-ring organic matter were correlated with those of leaf and twig water and with plant physiological traits across treatments and species. The 2H-enrichment in plant organic matter also went along with a decrease in stem starch concentrations under soil drought compared with well-watered conditions. In contrast, the predisposing fertilization had generally no significant effect on any tested isotopic, physiological and metabolic traits. We propose that the 2H-enrichment in the dead trees is related to (i) the plant water isotopic composition, (ii) metabolic processes shaping leaf non-structural carbohydrates, (iii) the use of carbon reserves for growth and (iv) species-specific physiological adjustments. The homogenous stress imprint on δ2H but not on δ18O suggests that the former could be used as a proxy to reconstruct soil droughts and underlying processes of tree mortality.
Topics: Plant Leaves; Droughts; Trees; Soil; Oxygen Isotopes; Water; Deuterium; Plant Stems
PubMed: 38618738
DOI: 10.1093/treephys/tpae043 -
American Journal of Veterinary Research Jun 2024The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers...
OBJECTIVE
The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers also associated with the metabolic dysfunction that occurs with natural aging.
ANIMALS
24 male Beagle dogs, 3 to 7 years of age, of mixed castration status.
METHODS
Dogs were randomly assigned to continue twice daily feeding of the commercial adult maintenance diet (n = 12, including 2 intact) that they were previously fed or to a high-fat diet (12, including 2 intact) for 17 weeks between December 1, 2021, and April 28, 2022. Assessments included body composition (weight, body condition score, and adipose mass determined by deuterium enrichment), clinical chemistries, plasma fatty acid quantification, oral glucose tolerance test, and histology of subcutaneous and visceral adipose biopsy samples.
RESULTS
The high-fat diet led to increased body weight, body condition score, fat mass and adipocyte size, hyperinsulinemia and peripheral insulin resistance, and elevations in serum lipids, including cholesterol, triglycerides, and several species of free fatty acids. Leptin levels increased in dogs fed a high-fat diet but not in control dogs. There were no significant changes in routine clinical chemistry values in either group.
CLINICAL RELEVANCE
Feeding a high-fat diet for 17 weeks led to potentially deleterious changes in metabolism similar to those seen in natural aging in dogs, including hyperinsulinemia, insulin resistance, and dyslipidemia. A high-fat diet model may provide insights into the similar metabolic dysfunction that occurs during natural aging.
Topics: Animals; Dogs; Male; Insulin Resistance; Diet, High-Fat; Hyperinsulinism; Dog Diseases; Dyslipidemias; Aging; Body Composition; Animal Feed; Random Allocation
PubMed: 38604223
DOI: 10.2460/ajvr.23.11.0253 -
Frontiers in Cellular Neuroscience 2024
PubMed: 38601024
DOI: 10.3389/fncel.2024.1401687