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Gut Microbes Dec 2023Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal...
Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of and , and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.
Topics: Infant; Female; Humans; Breast Feeding; Gastrointestinal Microbiome; Milk, Human; Microbiota; Oligosaccharides; Metabolome
PubMed: 37741856
DOI: 10.1080/19490976.2023.2257273 -
Scientific Data Sep 2023Metabolic stable isotope labeling with heavy water followed by liquid chromatography coupled with mass spectrometry (LC-MS) is a powerful tool for in vivo protein...
Metabolic stable isotope labeling with heavy water followed by liquid chromatography coupled with mass spectrometry (LC-MS) is a powerful tool for in vivo protein turnover studies. Several algorithms and tools have been developed to determine the turnover rates of peptides and proteins from time-course stable isotope labeling experiments. The availability of benchmark mass spectrometry data is crucial to compare and validate the effectiveness of newly developed techniques and algorithms. In this work, we report a heavy water-labeled LC-MS dataset from the murine liver for protein turnover rate analysis. The dataset contains eighteen mass spectral data with their corresponding database search results from nine different labeling durations and quantification outputs from d2ome+ software. The dataset also contains eight mass spectral data from two-dimensional fractionation experiments on unlabeled samples.
Topics: Animals; Mice; Chromatography, Liquid; Deuterium Oxide; Liver; Proteome; Tandem Mass Spectrometry
PubMed: 37726365
DOI: 10.1038/s41597-023-02537-w -
The Journal of Physical Chemistry. B Sep 2023DO is commonly used as a solvent instead of HO in spectroscopic studies of proteins, in particular, in infrared and nuclear-magnetic-resonance spectroscopy. DO is... (Review)
Review
DO is commonly used as a solvent instead of HO in spectroscopic studies of proteins, in particular, in infrared and nuclear-magnetic-resonance spectroscopy. DO is chemically equivalent to HO, and the differences, particularly in hydrogen-bond strength, are often ignored. However, replacing solvent water with DO can affect not only the kinetics but also the structure and stability of biomolecules. Recent experiments have shown that even the mesoscopic structures and the elastic properties of biomolecular assemblies, such as amyloids and protein networks, can be very different in DO and HO. We discuss these findings, which probably are just the tip of the iceberg, and which seem to call for obtaining a better understanding of the HO/DO-isotope effect on water-water and water-protein interactions. Such improved understanding may change the differences between HO and DO as biomolecular solvents from an elephant in the room to an opportunity for protein research.
Topics: Water; Proteins; Solvents; Isotopes; Deuterium Oxide
PubMed: 37722111
DOI: 10.1021/acs.jpcb.3c04385 -
Chemical Science Sep 2023Cucurbit[7]uril (CB[7]) encapsulates adamantyl and trimethylsilyl substituents of positively charged guests in dimethyl sulfoxide (DMSO). Unlike in water or deuterium...
Cucurbit[7]uril (CB[7]) encapsulates adamantyl and trimethylsilyl substituents of positively charged guests in dimethyl sulfoxide (DMSO). Unlike in water or deuterium oxide, addition of a selection of alkali and alkali-earth cations with van der Waals radii between 1.0 and 1.4 Å (Na, K, Ca, Sr, Ba and Eu) to the CB[7]/guest complexes triggers their cation-mediated trimerization, a process that is very slow on the nuclear magnetic resonance (NMR) time scale. Smaller (Li, Mg) or larger cations (Rb, Cs or NH) are inert. The trimers display extensive CH-O interactions between the equatorial and pseudo-equatorial hydrogens of CB[7] and the carbonyl rim of the neighboring CB[7] unit in the trimer, and a deeply nested cation between the three interacting carbonylated CB[7] rims; a counteranion is likely perched in the shallow cavity formed by the three outer walls of CB[7] in the trimer. Remarkably, a guest must occupy the cavity of CB[7] for trimerization to take place. Using a combination of semi-empirical and density functional theory techniques in conjunction with continuum solvation models, we showed that trimerization is favored in DMSO, and not in water, because the penalty for the partial desolvation of three of the six CB[7] portals upon aggregation into a trimer is less unfavorable in DMSO compared to water.
PubMed: 37712024
DOI: 10.1039/d3sc02032k -
Frontiers in Nutrition 2023To date, body composition assessments in Hispanics, computed via bioimpedance devices, have primarily focused on body fat percent, fat mass, and fat-free mass instead of...
BACKGROUND
To date, body composition assessments in Hispanics, computed via bioimpedance devices, have primarily focused on body fat percent, fat mass, and fat-free mass instead of total body water (TBW). Additionally, virtually no information is available on which type of bioimpedance device is preferred for TBW assessments in Hispanic populations.
PURPOSE
The purpose of this study was to validate two bioimpedance devices for the estimate of TBW in Hispanics adults when using a criterion deuterium oxide (DO) technique.
METHODS
One-hundred thirty individuals (males: = 70; females: = 60) of Hispanic descent had TBW estimated via DO, single-frequency bioimpedance analysis ([SF-BIA] Quantum V, RJL Systems) and bioimpedance spectroscopy ([BIS] SFB7 Impedimed).
RESULTS
The mean values for SF-BIA were significantly lower than DO when evaluating the entire sample (37.4 L and 38.2 L, respectively; < 0.05). In contrast, TBW values were not statistically significant when comparing DO against BIS (38.4 L, > 0.05). Bland-Altman analysis indicated no proportional bias when evaluating the entire sample for SF-BIA or BIS. The standard error of estimate and total error values were ≤ 2.3 L and Lin's concordance correlation coefficient were ≥ 0.96 for all comparisons.
CONCLUSION
The SF-BIA and BIS devices evaluated in the current study hold promise for accurate estimation of TBW in Hispanic adults. While both methods demonstrated relatively low errors relative to the DO criterion, BIS exhibited a more consistent performance, particularly at the group level. These findings provide essential information for researchers and clinical nutrition practitioners assessing TBW in Hispanic adults.
PubMed: 37693242
DOI: 10.3389/fnut.2023.1221774 -
Infection and Drug Resistance 2023Antibiotic resistance represents a serious global health challenge, particularly with the emergence of strains resistant to last-resort antibiotics such as tigecycline,...
BACKGROUND
Antibiotic resistance represents a serious global health challenge, particularly with the emergence of strains resistant to last-resort antibiotics such as tigecycline, polymyxin B, and vancomycin. Urgent measures are required to alleviate this situation. To facilitate the judicious use of antibiotics, rapid and precise antimicrobial susceptibility testing (AST) is essential. Heavy water (deuterium oxide, DO)-labeled Raman spectroscopy has emerged as a promising time-saving tool for microbiological testing.
METHODS
Deuterium incorporation and experimental conditions were examined to develop and apply a Raman-based AST method to evaluate the efficacy of last-resort antibiotics, including tigecycline, polymyxin B, and vancomycin, against , and . Essential agreement and categorical agreement were used to assess the metabolism inactivation concentration based on Raman spectroscopy (R-MIC)-a new metric developed in this study-and minimum inhibitory concentration (MIC) determined via the traditional microdilution broth method. Spearman's rank correlation coefficient was employed to measure the association between R-MIC and MIC values.
RESULTS
The Raman-based AST method achieved a 100% categorical agreement (92/92) with the traditional microdilution broth method within five hours, while the traditional method required approximately 24 h. The R-MIC values shared 68.5% (63/92) consistency with the MIC values. In addition, the R-MIC and MIC values were highly correlated (Spearman's r=0.96), resulting in an essential agreement of 100%.
CONCLUSION
Our optimized experimental method and conditions indicate that Raman-based AST holds great promise as a solution to overcome the time-consuming challenges of traditional AST methods.
PubMed: 37638072
DOI: 10.2147/IDR.S404732 -
RSC Advances Aug 2023Heavy water is known to affect many different biological systems, with the most striking effects observed at the cellular level. Many dynamic processes, such as...
Heavy water is known to affect many different biological systems, with the most striking effects observed at the cellular level. Many dynamic processes, such as migration or invasion, but also central processes of cell proliferation are measurably inhibited by the presence of deuterium oxide (DO). Furthermore, individual cell deformabilities are significantly decreased upon DO treatment. In order to understand the origin of these effects, we studied entangled filamentous actin networks, a commonly used model system for the cytoskeleton, which is considered a central functional element for dynamic cellular processes. Using bulk shear rheology to extract rheological signatures of reconstituted actin networks at varying concentrations of DO, we found a non-monotonic behavior, which is explainable by a drastic change in the actin network architecture. Applying light scattering and fluorescence microscopy, we were able to demonstrate that the presence of deuterium oxide induces bundling in reconstituted entangled networks of filamentous actin. This constitutes an entirely novel and previously undescribed actin bundling mechanism.
PubMed: 37601592
DOI: 10.1039/d3ra03917j -
Journal of Cachexia, Sarcopenia and... Oct 2023Skeletal muscle mass and strength diminish during periods of disuse but recover upon return to weight bearing in healthy adults but are incomplete in old muscle. Efforts...
BACKGROUND
Skeletal muscle mass and strength diminish during periods of disuse but recover upon return to weight bearing in healthy adults but are incomplete in old muscle. Efforts to improve muscle recovery in older individuals commonly aim at increasing myofibrillar protein synthesis via mammalian target of rapamycin (mTOR) stimulation despite evidence demonstrating that old muscle has chronically elevated levels of mammalian target of rapamycin complex 1 (mTORC1) activity. We hypothesized that protein synthesis is higher in old muscle than adult muscle, which contributes to a proteostatic stress that impairs recovery.
METHODS
We unloaded hindlimbs of adult (10-month) and old (28-month) F344BN rats for 14 days to induce atrophy, followed by reloading up to 60 days with deuterium oxide (D O) labelling to study muscle regrowth and proteostasis.
RESULTS
We found that old muscle has limited recovery of muscle mass during reloading despite having higher translational capacity and myofibrillar protein synthesis (0.029 k/day ± 0.002 vs. 0.039 k/day ± 0.002, P < 0.0001) than adult muscle. We showed that collagen protein synthesis was not different (0.005 k (1/day) ± 0.0005 vs. 0.004 k (1/day) ± 0.0005, P = 0.15) in old compared to adult, but old muscle had higher collagen concentration (4.5 μg/mg ± 1.2 vs. 9.8 μg/mg ± 0.96, P < 0.01), implying that collagen breakdown was slower in old muscle than adult muscle. This finding was supported by old muscle having more insoluble collagen (4.0 ± 1.1 vs. 9.2 ± 0.9, P < 0.01) and an accumulation of advanced glycation end products (1.0 ± 0.06 vs. 1.5 ± 0.08, P < 0.001) than adult muscle during reloading. Limited recovery of muscle mass during reloading is in part due to higher protein degradation (0.017 1/t ± 0.002 vs. 0.028 1/t ± 0.004, P < 0.05) and/or compromised proteostasis as evidenced by accumulation of ubiquitinated insoluble proteins (1.02 ± 0.06 vs. 1.22 ± 0.06, P < 0.05). Last, we showed that synthesis of individual proteins related to protein folding/refolding, protein degradation and neural-related biological processes was higher in old muscle during reloading than adult muscle.
CONCLUSIONS
Our data suggest that the failure of old muscle to recover after disuse is not due to limitations in the ability to synthesize myofibrillar proteins but because of other impaired proteostatic mechanisms (e.g., protein folding and degradation). These data provide novel information on individual proteins that accumulate in protein aggregates after disuse and certain biological processes such as protein folding and degradation that likely play a role in impaired recovery. Therefore, interventions to enhance regrowth of old muscle after disuse should be directed towards the identified impaired proteostatic mechanisms and not aimed at increasing protein synthesis.
Topics: Humans; Rats; Animals; Aged; Muscular Atrophy; Aging; Muscle, Skeletal; Muscular Disorders, Atrophic; TOR Serine-Threonine Kinases; Collagen; Mammals
PubMed: 37448295
DOI: 10.1002/jcsm.13285 -
Nature Communications Jul 2023Separating deuterium from hydrogen isotope mixtures is of vital importance to develop nuclear energy industry, as well as other isotope-related advanced technologies. As...
Separating deuterium from hydrogen isotope mixtures is of vital importance to develop nuclear energy industry, as well as other isotope-related advanced technologies. As one of the most promising alternatives to conventional techniques for deuterium purification, kinetic quantum sieving using porous materials has shown a great potential to address this challenging objective. From the knowledge gained in this field; it becomes clear that a quantum sieve encompassing a wide range of practical features in addition to its separation performance is highly demanded to approach the industrial level. Here, the rational design of an ultra-microporous squarate pillared titanium oxide hybrid framework has been achieved, of which we report the comprehensive assessment towards practical deuterium separation. The material not only displays a good performance combining high selectivity and volumetric uptake, reversible adsorption-desorption cycles, and facile regeneration in adsorptive sieving of deuterium, but also features a cost-effective green scalable synthesis using chemical feedstock, and a good stability (thermal, chemical, mechanical and radiolytic) under various working conditions. Our findings provide an overall assessment of the material for hydrogen isotope purification and the results represent a step forward towards next generation practical materials for quantum sieving of important gas isotopes.
Topics: Deuterium; Adsorption; Biological Transport; Hydrogen
PubMed: 37443163
DOI: 10.1038/s41467-023-39871-x -
Molecular & Cellular Proteomics : MCP Aug 2023Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight into disease mechanisms underpinned by post-transcriptional processes. We used...
Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight into disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; DO) labeling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from two individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4420 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample. FSHD myoblasts exhibited a greater abundance but slower turnover rate of subunits of mitochondrial respiratory complexes and mitochondrial ribosomal proteins, which may indicate an accumulation of "older" less viable mitochondrial proteins in myoblasts from individuals affected by FSHD. Treatment with a 2'-O-methoxyethyl modified antisense oligonucleotide targeting exon 3 of the double homeobox 4 (DUX4) transcript tended to reverse mitochondrial protein dysregulation in FSHD myoblasts, indicating the effect on mitochondrial proteins may be a DUX4-dependent mechanism. Our results highlight the importance of post-transcriptional processes and protein turnover in FSHD pathology and provide a resource for the FSHD research community to explore this burgeoning aspect of FSHD.
Topics: Humans; Muscular Dystrophy, Facioscapulohumeral; Proteome; Proteomics; Homeodomain Proteins; Myoblasts; Muscle, Skeletal
PubMed: 37353005
DOI: 10.1016/j.mcpro.2023.100605