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The Journal of Nutrition Jun 2023It remains unclear whether non-animal-derived dietary protein sources (and therefore vegan diets) can support resistance training-induced skeletal muscle remodeling to... (Clinical Trial)
Clinical Trial
BACKGROUND
It remains unclear whether non-animal-derived dietary protein sources (and therefore vegan diets) can support resistance training-induced skeletal muscle remodeling to the same extent as animal-derived protein sources.
METHODS
In Phase 1, 16 healthy young adults (m = 8, f = 8; age: 23 ± 1 y; BMI: 23 ± 1 kg/m) completed a 3-d dietary intervention (high protein, 1.8 g·kg bm·d) where protein was derived from omnivorous (OMNI1; n = 8) or exclusively non-animal (VEG1; n = 8) sources, alongside daily unilateral leg resistance exercise. Resting and exercised daily myofibrillar protein synthesis (MyoPS) rates were assessed using deuterium oxide. In Phase 2, 22 healthy young adults (m = 11, f = 11; age: 24 ± 1 y; BMI: 23 ± 0 kg/m) completed a 10 wk, high-volume (5 d/wk), progressive resistance exercise program while consuming an omnivorous (OMNI2; n = 12) or non-animal-derived (VEG2; n = 10) high-protein diet (∼2 g·kg bm·d). Muscle fiber cross-sectional area (CSA), whole-body lean mass (via DXA), thigh muscle volume (via MRI), muscle strength, and muscle function were determined pre, after 2 and 5 wk, and postintervention.
OBJECTIVES
To investigate whether a high-protein, mycoprotein-rich, non-animal-derived diet can support resistance training-induced skeletal muscle remodeling to the same extent as an isonitrogenous omnivorous diet.
RESULTS
Daily MyoPS rates were ∼12% higher in the exercised than in the rested leg (2.46 ± 0.27%·d compared with 2.20 ± 0.33%·d and 2.62 ± 0.56%·d compared with 2.36 ± 0.53%·d in OMNI1 and VEG1, respectively; P < 0.001) and not different between groups (P > 0.05). Resistance training increased lean mass in both groups by a similar magnitude (OMNI2 2.6 ± 1.1 kg, VEG2 3.1 ± 2.5 kg; P > 0.05). Likewise, training comparably increased thigh muscle volume (OMNI2 8.3 ± 3.6%, VEG2 8.3 ± 4.1%; P > 0.05), and muscle fiber CSA (OMNI2 33 ± 24%, VEG2 32 ± 48%; P > 0.05). Both groups increased strength (1 repetition maximum) of multiple muscle groups, to comparable degrees.
CONCLUSIONS
Omnivorous and vegan diets can support comparable rested and exercised daily MyoPS rates in healthy young adults consuming a high-protein diet. This translates to similar skeletal muscle adaptive responses during prolonged high-volume resistance training, irrespective of dietary protein provenance. This trial was registered at clinicaltrials.gov as NCT03572127.
Topics: Humans; Diet, High-Protein; Diet, Vegan; Dietary Proteins; Hypertrophy; Muscle Strength; Muscle, Skeletal; Resistance Training; Vegans
PubMed: 36822394
DOI: 10.1016/j.tjnut.2023.02.023 -
Nature Methods Mar 2023Stimulated Raman scattering (SRS) offers the ability to image metabolic dynamics with high signal-to-noise ratio. However, its spatial resolution is limited by the...
Stimulated Raman scattering (SRS) offers the ability to image metabolic dynamics with high signal-to-noise ratio. However, its spatial resolution is limited by the numerical aperture of the imaging objective and the scattering cross-section of molecules. To achieve super-resolved SRS imaging, we developed a deconvolution algorithm, adaptive moment estimation (Adam) optimization-based pointillism deconvolution (A-PoD) and demonstrated a spatial resolution of lower than 59 nm on the membrane of a single lipid droplet (LD). We applied A-PoD to spatially correlated multiphoton fluorescence imaging and deuterium oxide (DO)-probed SRS (DO-SRS) imaging from diverse samples to compare nanoscopic distributions of proteins and lipids in cells and subcellular organelles. We successfully differentiated newly synthesized lipids in LDs using A-PoD-coupled DO-SRS. The A-PoD-enhanced DO-SRS imaging method was also applied to reveal metabolic changes in brain samples from Drosophila on different diets. This new approach allows us to quantitatively measure the nanoscopic colocalization of biomolecules and metabolic dynamics in organelles.
Topics: Microscopy; Spectrum Analysis, Raman; Proteins; Lipids
PubMed: 36797410
DOI: 10.1038/s41592-023-01779-1 -
The American Journal of Clinical... Apr 2023Human milk provides essential nutrition for infants, and its benefits are well established. We lack data on the influence of maternal nutritional status on milk volume... (Observational Study)
Observational Study
BACKGROUND
Human milk provides essential nutrition for infants, and its benefits are well established. We lack data on the influence of maternal nutritional status on milk volume and composition in low-middle income countries.
OBJECTIVE
We aimed to 1) assess lactation performance (human milk volume, macronutrient composition, and infant energy intake) in Indian females and 2) examine the associations between maternal anthropometry (BMI, percentage body fat) and lactation performance.
METHODS
We conducted an observational study among 232 mother-infant dyads, 2 to 4 mo postpartum in Haryana, India. We used deuterium oxide dose-to-mother technique to measure milk volume and maternal percentage body fat and collected human milk samples to determine macronutrient and energy concentrations. Adjusted multiple linear regression models were used to examine the associations between maternal anthropometry and lactation performance.
RESULTS
The mean BMI and percentage body fat of mothers were 21.7 ± 3.6 kg/m and 29.5 ± 7.7, respectively. Milk volume and macronutrient composition were similar to the reference values (means ± standard deviations: milk volume, 724 ± 184 mL/d; median (25th, 75th percentile); protein, 9.9 (8.3, 11.7) g/L; fat, 41.0 ± 15.2 g/L; energy density, 0.71 ± 0.14 kcal/g; lactose, 65.5 (55.3, 71.3) g/L). Maternal BMI and percentage body fat were not significantly associated with macronutrient composition. Both maternal BMI and percentage body fat were negatively associated with milk volume (-7.0, 95% CI: -12.4, -1.6 mL/d; -3.5, 95% CI: -6.0, -1.1mL/d, respectively) but there were no effects on the total energy intake of infants after adjusting for covariates.
CONCLUSION
Most mothers had a normal BMI and milk of similar composition and volume to reference values. Future work in populations with a greater burden of underweight and/or obesity are needed to examine the underlying mechanisms between maternal body composition and milk volume. This trial was registered at The Clinical Trials Registry- India as CTRI/2017/01/007636.
Topics: Female; Infant; Humans; Nutritional Status; Lactation; Milk, Human; Body Composition; Energy Intake
PubMed: 36773786
DOI: 10.1016/j.ajcnut.2023.02.002 -
Molecules (Basel, Switzerland) Jan 2023Pyrrolopyrimidines are important scaffolds for the preparation of bioactive molecules. Therefore, developing efficient and flexible ways for selective functionalization...
Pyrrolopyrimidines are important scaffolds for the preparation of bioactive molecules. Therefore, developing efficient and flexible ways for selective functionalization of the pyrrolopyrimidine skeleton is of interest. We have investigated lithiation-addition at C-6 of protected 4-chloro-7-pyrrolo [2,3-]pyrimidine as a route to new building blocks for medicinal chemistry. It was found that bis(2-dimethylaminoethyl) ether as an additive increased the yield in the additional reaction with benzaldehyde. Deuterium oxide quench experiments showed that this additive offered both a higher degree of lithiation and increased stability of the lithiated intermediate. The substrate scope of the protocol was investigated with 16 aldehydes and ketones, revealing the method to be excellently suited for reaction with aldehydes, cyclohexanone derivatives and 2,2,2-trifluoroacetophenone, while being less efficient for acetophenones. Yields in the range of 46-93% were obtained.
PubMed: 36770597
DOI: 10.3390/molecules28030932 -
Magnetic Resonance in Medicine Jun 2023To quantify the variations of the power-law dependences on diffusion time t or gradient frequency of extracellular water diffusion measured by diffusion MRI (dMRI).
PURPOSE
To quantify the variations of the power-law dependences on diffusion time t or gradient frequency of extracellular water diffusion measured by diffusion MRI (dMRI).
METHODS
Model cellular systems containing only extracellular water were used to investigate the dependence of , the extracellular diffusion coefficient. Computer simulations used a randomly packed tissue model with realistic intracellular volume fractions and cell sizes. DMRI measurements were performed on samples consisting of liposomes containing heavy water(D O, deuterium oxide) dispersed in regular water (H O). was obtained over a broad range (∼1-1000 ms) and then fit power-law equations and .
RESULTS
Both simulated and experimental results suggest that no single power-law adequately describes the behavior of over the range of diffusion times of most interest in practical dMRI. Previous theoretical predictions are accurate over only limited ranges; for example, is valid only for short times, whereas or is valid only for long times but cannot describe other ranges simultaneously. For the specific range of 5-70 ms used in typical human dMRI measurements, matches the data well empirically.
CONCLUSION
The optimal power-law fit of extracellular diffusion varies with diffusion time. The dependency obtained at short or long limits cannot be applied to typical dMRI measurements in human cancer or liver. It is essential to determine the appropriate diffusion time range when modeling extracellular diffusion in dMRI-based quantitative microstructural imaging.
Topics: Humans; Diffusion Magnetic Resonance Imaging; Neoplasms; Diffusion; Models, Biological; Computer Simulation
PubMed: 36740894
DOI: 10.1002/mrm.29594 -
Angewandte Chemie (International Ed. in... Apr 2023Interest in deuterated active pharmaceutical ingredients (APIs) is increasing as deuteration holds promise for kinetic isotope effect (KIE) regulated fine-tuning of API...
Interest in deuterated active pharmaceutical ingredients (APIs) is increasing as deuteration holds promise for kinetic isotope effect (KIE) regulated fine-tuning of API performance. Moreover, deuterium isotope labeling is frequently carried out to study organic and bioorganic reaction mechanisms and to facilitate complex target synthesis. As such, methods for highly selective deuteration of organic molecules are highly desirable. Herein, we present an electrochemical method for the selective deuterodehalogenation of benzylic halides via a radical-polar crossover mechanism, using inexpensive deuterium oxide (D O) as the deuterium source. We demonstrate broad functional group compatibility across a range of aryl and heteroaryl benzylic halides. Furthermore, we uncover a sequential paired electrolysis regime, which permits switching between net reductive and overall redox-neutral reactions of sulfur-containing substrates simply by changing the identity of the sacrificial reductant employed.
PubMed: 36738472
DOI: 10.1002/anie.202218858 -
Molecular Carcinogenesis May 2023Since its initial discovery as a natural isotopologue of dihydrogen oxide ( H O), extensive research has focused on the biophysical, biochemical, and pharmacological...
Systemic deuteration of SCID mice using the water-isotopologue deuterium oxide (D O) inhibits tumor growth in an orthotopic bioluminescent model of human pancreatic ductal adenocarcinoma.
Since its initial discovery as a natural isotopologue of dihydrogen oxide ( H O), extensive research has focused on the biophysical, biochemical, and pharmacological effects of deuterated water ( H O [D O, also referred to as "heavy water"]). Using a panel of cultured human pancreatic ductal adenocarcinoma (PDAC) cells we have profiled (i) D O-induced phenotypic antiproliferative and apoptogenic effects, (ii) redox- and proteotoxicity-directed stress response gene expression, and (iii) phosphoprotein-signaling related to endoplasmic reticulum (ER) and MAP-kinase stress response pathways. Differential array analysis revealed early modulation of stress response gene expression in both BxPC-3 and PANC-1 PDAC cells elicited by D O (90%; ≤6 h; upregulated: HMOX1, NOS2, CYP2E1, CRYAB, DDIT3, NFKBIA, PTGS1, SOD2, PTGS2; downregulated: RUNX1, MYC, HSPA8, HSPA1A) confirmed by independent RT-qPCR analysis. Immunoblot-analysis revealed rapid (≤6 h) onset of D O-induced MAP-kinase signaling (p-JNK, p-p38) together with ER stress response upregulation (p-eIF2α, ATF4, XBP1s, DDIT3/CHOP). Next, we tested the chemotherapeutic efficacy of D O-based drinking water supplementation in an orthotopic PDAC model employing firefly luciferase-expressing BxPC-3-FLuc cells in SCID mice. First, feasibility and time course of systemic deuteration (30% D O in drinking water; 21 days) were established using time-resolved whole-body proton magnetic resonance imaging and isotope-ratio mass spectrometry-based plasma (D/H)-analysis. D O-supplementation suppressed tumor growth by almost 80% with downregulated expression of PCNA, MYC, RUNX1, and HSP70 while increasing tumor levels of DDIT3/CHOP, HO-1, and p-eIF2α. Taken together, these data demonstrate for the first time that pharmacological induction of systemic deuteration significantly reduces orthotopic tumor burden in a murine PDAC xenograft model.
Topics: Humans; Animals; Mice; Core Binding Factor Alpha 2 Subunit; Mice, SCID; Deuterium Oxide; Drinking Water; Cell Line, Tumor; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Cell Proliferation; Apoptosis
PubMed: 36727657
DOI: 10.1002/mc.23509 -
The Journal of Physical Chemistry. B Feb 2023Light and heavy water are often used interchangeably in spectroscopic experiments with the tacit assumption that the structure of the investigated biomolecule does not...
Light and heavy water are often used interchangeably in spectroscopic experiments with the tacit assumption that the structure of the investigated biomolecule does not depend too much on employing one or the other solvent. While this may often be a good approximation, we demonstrate here using molecular dynamics simulations incorporating nuclear quantum effects via modification of the interaction potential that there are small but significant differences. Namely, as quantified and discussed in the present study, both proteins and biomembranes tend to be slightly more compact and rigid in DO than in HO, which reflects the stronger hydrogen bonding in the former solvent.
Topics: Water; Proteins; Deuterium Oxide; Thermodynamics; Solvents
PubMed: 36722049
DOI: 10.1021/acs.jpcb.2c08270 -
ACS Physical Chemistry Au Jan 2023This work investigates the acid sites in a commercial ZSM-5 zeolite catalyst by a combination of spectroscopic and physical methods. The Brønsted acid sites in such...
This work investigates the acid sites in a commercial ZSM-5 zeolite catalyst by a combination of spectroscopic and physical methods. The Brønsted acid sites in such catalysts are associated with the aluminum substituted into the zeolite lattice, which may not be identical to the total aluminum content of the zeolite. Inelastic neutron scattering spectroscopy (INS) directly quantifies the concentrations of Brønsted acid protons, silanol groups, and hydroxyl groups associated with extra-framework aluminum species. The INS measurements show that ∼50% of the total aluminum content of this particular zeolite is extra framework, a conclusion supported by solid-state NMR and ammonia temperature-programmed desorption (TPD) measurements. Evidence for the presence of extra-framework aluminum oxide species is also seen in neutron powder diffraction data from proton- and deuterium-exchanged samples. The differences between results from the different analytical methods are discussed, and the novelty of direct proton counting by INS in this typical commercial catalyst is emphasized.
PubMed: 36718264
DOI: 10.1021/acsphyschemau.2c00040 -
Journal of Proteome Research Feb 2023Retention time (RT) alignment has been important for robust protein identification and quantification in proteomics. In data-dependent acquisition mode, whereby the...
Retention time (RT) alignment has been important for robust protein identification and quantification in proteomics. In data-dependent acquisition mode, whereby the precursor ions are semistochastically chosen for fragmentation in MS/MS, the alignment is used in an approach termed matched between runs (MBR). MBR transfers peptides, which were fragmented and identified in one experiment, to a replicate experiment where they were not identified. Before the MBR transfer, the RTs of experiments are aligned to reduce the chance of erroneous transfers. Despite its widespread use in other areas of quantitative proteomics, RT alignment has not been applied in data analyses for protein turnover using an atom-based stable isotope-labeling agent such as metabolic labeling with deuterium oxide, DO. Deuterium incorporation changes isotope profiles of intact peptides in full scans and their fragment ions in tandem mass spectra. It reduces the peptide identification rates in current database search engines. Therefore, the MBR becomes more important. Here, we report on an approach to incorporate RT alignment with peptide quantification in studies of proteome turnover using heavy water metabolic labeling and LC-MS. The RT alignment uses correlation-optimized time warping. The alignment, followed by the MBR, improves labeling time point coverage, especially for long labeling durations.
Topics: Tandem Mass Spectrometry; Deuterium Oxide; Peptides; Proteome; Isotopes; Isotope Labeling
PubMed: 36692003
DOI: 10.1021/acs.jproteome.2c00592